question Flashcards
1
Q
What are the available options for the treatment of diabetes?
A
The available options for the treatment of diabetes include sulfonylureas, DPP4 inhibitors/GLP1 analogues, SGLT2 inhibitors, and α-glucosidase inhibitors.
2
Q
Why is pioglitazone contraindicated in heart failure patients?
A
Pioglitazone is contraindicated in heart failure patients as it worsens heart failure by stimulating sodium reabsorption from the collecting duct, leading to fluid retention.
3
Q
Which DPP4 inhibitor has been shown to increase the risk of heart failure?
A
Saxagliptin has been shown to increase the risk of heart failure.
4
Q
Do GLP1 analogues have a cardiovascular benefit?
A
GLP1 analogues have been shown to have a cardiovascular benefit, but limited data exists.
5
Q
What is the dosing schedule and time of administration of sulfonylureas?
A
The dosing schedule and time of administration of sulfonylureas are as follows: Glibenclamide - 10-20 mg once or twice daily, 30 minutes prior to a meal; Glipizide - 20-40 mg twice daily, 30 minutes prior to a meal; Gliclazide - 160-320 mg twice daily, 30 minutes prior to a meal; Glimepiride - 4-8 mg once or twice daily, 30 minutes prior to a meal.
6
Q
What is the time of administration for oral antidiabetic drugs?
A
The time of administration for oral antidiabetic drugs is as follows: Sulfonylureas - 30 minutes prior to a meal; Metformin - with or after meals; Acarbose/voglibose - just before major meals; Pioglitazone - before meals but at a fixed time; DPP4 inhibitors - prior to a meal; GLP1 agonists - prior to a meal.
7
Q
What is the HbA1c-reducing efficacy of various treatment modalities in the management of diabetes?
A
The HbA1c-reducing efficacy of various treatment modalities in the management of diabetes is as follows: Lifestyle modification - 1-2%; Sulfonylureas (SU) - 1-1.5%; Metformin - 1-1.5%; SU+metformin - 1-1.5%; Pioglitazone - 1-1.2%; DPP4 inhibitors - 0.6-0.8%; GLP1 agonists - 1-1.3%; Insulin - unlimited.
8
Q
What are the probabilities associated with sudden worsening of vision in a patient on metformin, sulfonylurea, and pioglitazone?
A
The sudden worsening of vision in a patient on metformin, sulfonylurea, and pioglitazone may be due to macular edema caused by pioglitazone. Other possibilities include retinal detachment, vitreous hemorrhage, and central retinal artery/vein occlusion.
9
Q
Is there a real risk for bladder cancer with pioglitazone?
A
There is a possible association between bladder cancer and the use of pioglitazone. The risk of bladder cancer is higher with a cumulative dose >28g and duration of use >2 years. However, some studies did not reveal an increased risk with pioglitazone use.
10
Q
What are some of the drugs available for the management of osteoporosis?
A
The available drugs for the management of osteoporosis are anabolic drugs (rPTH1-34 or rPTH1-84), calcilytics (CaSR), romosozumab (sclerostin), abaloparatide (rPTHrP1-34 analogue), estrogen and SERM, bisphosphonates, denosumab (RANKL antibody), odanacatib (cathepsin K inhibitor), and saracatinib (c-Src kinase inhibitor).
11
Q
How do bisphosphonates act?
A
Bisphosphonates (BPs) bind to calcium hydroxyapatite at active bone remodeling sites to exert their antiresorptive effects. They inhibit crystal dissolution and suppress bone resorption by blocking osteoclast action. BPs are classified into non-nitrogen-containing BPs and nitrogen-containing BPs, with each having different mechanisms of action.
12
Q
What is the mechanism of action of non-nitrogen-containing bisphosphonates?
A
Non-nitrogen-containing bisphosphonates, such as etidronate and clodronate analogues, are metabolically incorporated into non-hydrolyzable ATP analogues within osteoclasts, resulting in osteoclast apoptosis.
13
Q
What is the mechanism of action of nitrogen-containing bisphosphonates?
A
Nitrogen-containing bisphosphonates (amino-BPs), like pamidronate, alendronate, risedronate, ibandronate, and zoledronate, inhibit the mevalonate pathway by blocking farnesyl diphosphate synthase (FDPS). This leads to cytoskeletal abnormalities and disruption of prenylation of small GTPases in osteoclasts, causing osteoclast apoptosis.
14
Q
What are the precautions to be taken before administering bisphosphonates?
A
Before administering bisphosphonates, a detailed history, examination, and appropriate investigations should be conducted to rule out secondary causes of osteoporosis and establish a definite indication for bisphosphonate use. Vitamin D levels should be assessed and supplemented if deficient. Renal function should be assessed, and bisphosphonates should preferably be avoided if eGFR is <30 ml/min. Oral cavity should be examined for periodontal diseases/caries and treated before bisphosphonate therapy. Oral bisphosphonates should be avoided in those with upper gastrointestinal disease.
15
Q
Which bisphosphonate is preferred for the management of osteoporosis?
A
Zoledronate is the most potent bisphosphonate and is administered once a year, making it convenient for patients in clinical practice. However, all newer generation bisphosphonates are equally effective in preventing both hip and spine fractures.
16
Q
What adverse events are associated with bisphosphonate therapy?
A
The adverse events associated with bisphosphonate use include acute flu-like syndrome, GI intolerance (nausea, vomiting, diarrhea, esophagitis), hypocalcemia, hypophosphatemia, occasional atrial fibrillation, renal failure, severe suppression of bone turnover, atypical fractures, impaired bone remodeling, osteonecrosis of jaw, and rare cases of esophageal carcinoma.
17
Q
How do bisphosphonates cause hypocalcemia and hypophosphatemia?
A
The exact mechanism of how bisphosphonates cause hypocalcemia and hypophosphatemia is not described in the course notes.
18
Q
When is discontinuation of therapy mandated in the case of a rise in serum creatinine?
A
Discontinuation of therapy is mandated if the rise in serum creatinine is more than 30% or is associated with hyperkalemia.
19
Q
What are the causes of worsening renal function after initiation of ACEIs/ARBs?
A
The causes of worsening renal function after initiation of ACEIs/ARBs include bilateral renal artery stenosis, overzealous use of diuretics, accelerated hypertension, and uncontrolled hyperglycemia.
20
Q
How do ACEIs or ARBs prevent diabetes?
A
ACEIs/ARBs prevent new-onset diabetes by increasing skeletal muscle blood flow, upregulating IRS-2 mRNA expression, and inhibiting adipocyte RAAS. This leads to skeletal muscle vasodilatation, improved insulin delivery to muscle, increased IRS-2 mRNA expression, enhanced insulin signaling pathway, and differentiation of preadipocytes to smaller, more insulin-sensitive adipocytes.
21
Q
What is the likely diagnosis for a 60-year-old male with T2DM presenting with acute-onset lumbar pain, haematuria, and history of passage of flakes in urine?
A
The likely diagnosis is acute papillary necrosis, which is indicated by the presence of necrosed papilla and the passage of flakes in urine. Common precipitating factors include urinary tract infections and drugs like NSAIDs. In patients with diabetes, factors such as accelerated atherosclerosis, increased angiotensin II, and vulnerability to urinary tract infections can predispose to papillary necrosis.
22
Q
What are the modalities to preserve renal function in patients with DKD?
A
The modalities to preserve renal function in patients with DKD include good glycemic control (HbA1c <7%), optimal blood pressure control, use of ACEIs or ARBs, use of statins, correction of anemia, correction of metabolic acidosis, correction of secondary hyperparathyroidism, prevention of urinary tract infections, and the use of additional drugs like pioglitazone, linagliptin, and statins to reduce proteinuria.
23
Q
What are the causes of hypertension in diabetes?
A
The causes of hypertension in diabetes include essential hypertension (in the majority of patients with T2DM), hyperinsulinemia/insulin resistance, diabetic kidney disease, renal artery stenosis, and autonomic neuropathy. Almost 50% of patients with T2DM are hypertensive at the time of diabetes diagnosis, and 80-90% of diabetics become hypertensive with the development of proteinuria.
24
Q
How does insulin resistance cause hypertension?
A
Insulin resistance/hyperinsulinemia plays a role in the development of essential hypertension and T2DM. It increases blood pressure by promoting sodium and water reabsorption, enhancing intracellular movement of calcium, causing endothelial dysfunction, and reducing the vasodilatory effect of insulin in an insulin-resistant state.
25
What is the drug of choice for the management of hypertension?
The drug of choice for the management of hypertension is not specified in the provided course notes.
26
What is the recommended treatment for TIO?
Complete surgical excision of a well-localized tumor with wide margins is curative. If the tumor is inaccessible, radiofrequency ablation and lutetium-based therapies are other alternatives. In situations where the tumor is not localized, phosphate supplementation along with calcitriol is useful in the management of osteomalacia. Calcitriol helps in maintaining serum phosphate level by stimulating intestinal phosphate absorption and inhibiting renal phosphate wasting, which occurs as a result of phosphate therapy-induced rise in PTH. Calcimimetic agents like cinacalcet have been tried with limited success. Recently, a case report showed resolution of hypophosphatemia after total parathyroidectomy, and this opens new vistas in the management of TIO. Anti-FGF23 antibodies have been found to be effective in mouse models of hypophosphatemic osteomalacia and may be a promising alternative in the future.
27
What are the endocrine disorders associated with McCune–Albright syndrome?
McCune–Albright syndrome is associated with fibrous dysplasia, cafe-au-lait macules, and endocrinopathies. The common endocrine disorders include gonadotropin-independent precocious puberty, toxic nodular goiter, acrogigantism, and hypophosphatemic rickets/osteomalacia.
28
How does vitamin D deficiency impact fracture risk?
Vitamin D deficiency is an independent risk factor for fracture.
29
When should universal screening for vitamin D deficiency be recommended?
Ideally, screening for vitamin D deficiency should be done prior to vitamin D replacement. However, due to the rampant prevalence of vitamin D deficiency and its association with fracture risk, in routine clinical practice, supplementation without screening is recommended. Estimation of 25(OH)D is indicated in specific patient populations.
30
What are the indications for calcitriol therapy?
Calcitriol therapy is indicated in disorders associated with impaired 1α-hydroxylase activity or deficient secretion/action of PTH or increased FGF23. These include chronic kidney disease, hypoparathyroidism, pseudohypoparathyroidism, hypophosphatemic osteomalacia, renal tubular acidosis, hungry bone syndrome, and vitamin D-dependent rickets (type 1 and type 2). Elderly subjects may require calcitriol supplementation for bone health.
31
What is the role of PTH and FGF23 in regulating 1α-hydroxylase activity?
PTH and FGF23 are the prime regulators of 1α-hydroxylase activity. Impaired 1α-hydroxylase activity or deficient secretion/action of PTH or increased FGF23 can lead to disorders that require calcitriol therapy.
32
What are the alternate treatment options for TIO when the tumor is inaccessible?
When the tumor is inaccessible, radiofrequency ablation and lutetium-based therapies are other alternative treatment options for TIO.
33
What is the significance of hyperphosphatemia in a patient with McCune–Albright syndrome?
Hyperphosphatemia in a patient with McCune–Albright syndrome should prompt evaluation for hypersomatotropism.
34
What are the advantages of using HbA1c for the diagnosis of diabetes?
HbA1c has numerous advantages over blood glucose for the diagnosis of diabetes. It is a marker of chronic hyperglycemia, has greater pre-analytical stability, does not require fasting or administration of glucose load, and can be taken at any time of day.
35
What are the disadvantages of using HbA1c for the diagnosis of diabetes?
The disadvantages of HbA1c for the diagnosis of diabetes include lower diagnostic sensitivity, increased cost, limited utility in the presence of certain medical conditions (such as hemoglobinopathies, anemia, azotemia, and pregnancy), ethnic variability, and the need for standardization according to the DCCT/UKPDS standards.
36
In which patients should HbA1c not be used for the diagnosis of diabetes?
HbA1c is less reliable for the diagnosis of diabetes in patients with short duration of hyperglycemia, anemia, azotemia, hemoglobinopathies, and pregnant women.
37
What is considered the reference standard for the diagnosis of diabetes?
The 2-h PG post-glucose load >200mg/dl is considered the reference standard for the diagnosis of diabetes, as it best correlates with diabetic retinopathy, macrovascular disease, and HbA1c. However, it is cumbersome, has poor reproducibility, and is mainly used for research purposes.
38
What are the sensitivity and specificity of fasting plasma glucose compared to the reference standard for the diagnosis of diabetes?
The sensitivity of fasting plasma glucose is 50% and the specificity is 95% compared to the reference standard (2-h plasma glucose post-glucose load) for the diagnosis of diabetes.
39
What are the sensitivity and specificity of HbA1c (cutoff ≥6.5%) compared to the reference standard for the diagnosis of diabetes?
The sensitivity of HbA1c (cutoff ≥6.5%) is 44% and the specificity is 79% compared to the reference standard (2-h plasma glucose post-glucose load) for the diagnosis of diabetes.
40
How should an HbA1c of 6.2% and an FPG of 128 mg/dl be interpreted?
An HbA1c cutoff of 6.5% has a sensitivity of 44% to establish the diagnosis of diabetes, while FPG has a sensitivity of 50% in relation to the standard reference test. In this case, a repeat FPG and HbA1c should be performed. The repeat FPG was 130 mg/dl and the HbA1c was 6.3%. Therefore, the diagnosis of diabetes should be considered as 2 values of FPG are >126 mg/dl.
41
Who should be screened for diabetes?
Screening for type 2 diabetes is recommended in all adults who are overweight and have one additional risk factor, such as sedentary lifestyle, dyslipidemia, hypertension, cardiovascular disease, and family history of diabetes. It is also recommended in women with previous history of gestational diabetes, macrosomia, or polycystic ovarian disease. Screening is also indicated in all adults >45 years of age, irrespective of risk factors.
42
What is the rationale behind weekly levothyroxine therapy?
The rationale behind weekly levothyroxine therapy is based on the fact that LT4 has a half-life of 7 days. In a weekly regimen, seven times higher dose than the daily dose of levothyroxine is administered as a single dose once per week.
43
What was observed in the recent study comparing weekly and daily regimens of levothyroxine?
In the recent study, there was no difference in serum TSH levels achieved with both the regimens, but free T4 levels were significantly higher in the initial 4 h after administration of LT4 with a weekly regimen. However, this increase in free T4 levels was not accompanied by any symptoms of thyrotoxicosis or cardiac dysfunction.
44
Why is weekly regimen of levothyroxine not recommended?
The long-term safety data, particularly in elderly individuals, are not available; therefore, the weekly regimen is currently not recommended.
45
What are anti-mouse antibodies?
Anti-mouse antibodies, specifically human anti-mouse antibodies (HAMA), are antibodies produced in humans due to contact with animals or vaccination containing animal immunoglobulins. They are IgG in nature and interfere with TSH assays, leading to falsely high TSH value in the absence of primary thyroid dysfunction.
46
Why do newer TSH assays include blocking reagents like polymerized murine IgG?
Newer TSH assays include blocking reagents like polymerized murine IgG to overcome the interference caused by anti-mouse antibodies (HAMA) in the assay, which can lead to falsely high TSH values in the absence of primary thyroid dysfunction.
47
What is the role of iodine supplementation in patients with hypothyroidism?
Iodine supplementation in patients with hypothyroidism on levothyroxine replacement has no added advantage in improving thyroid function. However, routine iodized salt intake should be continued as iodine has many extrathyroidal advantages, including improvement in pregnancy outcome, antioxidant and anticancer properties, and suppression of autoimmunity.
48
What is the treatment of choice for hypothyroidism due to iodine deficiency?
Levothyroxine is the treatment of choice for hypothyroidism due to iodine deficiency. Therapeutic doses of stable iodine should be avoided in these patients to prevent Jod–Basedow’s phenomenon, as long-standing iodine deficiency may harbor thyroid nodules. Iodine supplementation in the form of iodized salt should be continued.
49
What is the preferred medium to deliver recommended daily allowance for iodine?
Common salt is the preferred medium to deliver the recommended daily allowance for iodine. The usual concentration of iodide in salt is 15–20 ppm (1 ppm is equivalent to 1 mg per kg). To provide the RDA of 150 μg iodine with a strength of 20 ppm, an intake of 10 g salt per day is required, which will be approximately equivalent to 150 μg of elemental iodine.
50
What are the pleiotropic effects of statins?
Statins have numerous pleiotropic effects including stabilization of coronary plaques, reduction in proteinuria, resolution of retinal hard exudates, increase in bone mineral density, and antioxidant/anti-inflammatory effects.
51
What is statin-induced myopathy?
Statin-induced myopathy is a condition where patients who receive statins experience muscle-related symptoms, such as myalgia or myositis, with elevated levels of creatine phosphokinase (CPK). Rarely, rhabdomyolysis can occur with the use of statins, characterized by extremely high CPK levels and a rise in serum creatinine.
52
What are the mechanisms for statin-induced myopathy?
The mechanism of statin-induced myopathy is not completely understood. However, theories propose that statins may result in mitochondrial dysfunction, depletion of isoprenoids, decrease in myocyte membrane cholesterol content, and increased expression of atrogin1, which decreases MyoD critical for muscle protein synthesis.
53
Who are at risk for statin-induced myopathy?
Those at risk for statin-induced myopathy include individuals with vitamin D deficiency, hypothyroidism, chronic alcoholism, older age (>80 years), strenuous physical activity, liver and renal disease, and those taking drugs like fibrates, ketoconazole, or macrolide antibiotics.
54
How can statin-induced myopathy be managed?
In patients experiencing mild and tolerable symptoms with CPK elevation <10-fold, statin therapy can be continued. If symptoms are intolerable and CPK elevation is <10-fold, switching to hydrophilic statins is recommended. Adequate treatment for concurrent vitamin D deficiency and hypothyroidism should be given. Discontinuation of statin therapy is necessary in case of CPK elevation >10-fold or rhabdomyolysis.
55
Does the use of statins cause diabetes?
Yes, the use of statins is associated with an increased incidence of new-onset diabetes. The risk of developing diabetes is dose dependent, greater in elderly individuals, and is a class effect, although some studies with pravastatin have shown a decreased risk of diabetes.
56
What is the estimated relative risk of developing diabetes with the use of statins?
The estimated relative risk of developing diabetes with the use of statins is 9%.
57
How many patients need to be treated with statins for 4 years to cause one additional case of new-onset diabetes?
A recent meta-analysis showed that 255 patients need to be treated with statins for 4 years to cause one additional case of new-onset diabetes. However, this treatment also resulted in the prevention of 5.4 cardiovascular events.
58
What are the extra-thyroidal manifestations of autoimmune thyroid diseases?
The extra-thyroidal manifestations of autoimmune thyroid disease include thyroid-associated orbitopathy, infiltrative dermopathy, and thyroid acropachy.
59
What is thyroid-associated orbitopathy?
Thyroid-associated orbitopathy (TAO) is an autoimmune disorder characterized by immuno-inflammation of the extraocular muscles and retro-orbital tissue, and invariably occurs in the presence of autoimmune thyroid disease, irrespective of presence of hyper-, hypo-, or euthyroidism.
60
Is there any difference between Graves’ orbitopathy and thyroid-associated orbitopathy?
Yes. The term thyroid-associated orbitopathy denotes orbitopathy associated with autoimmune thyroid disease, either Graves’ or Hashimoto’s thyroiditis, while Graves’ orbitopathy is a specific term for orbitopathy associated with Graves’ disease.
61
Is Graves’ ophthalmopathy and Graves’ orbitopathy synonymous?
No. Although the terms Graves’ ophthalmopathy and Graves’ orbitopathy are used interchangeably, they are not synonymous. The ocular manifestation in patients with thyroid disorder is due to involvement of retro-orbital tissue and ocular muscles. Therefore, the term “Graves’ ophthalmopathy” is a misnomer as it does not address orbital involvement in the disease process. Hence, the appropriate term should be Graves’ orbitopathy.
62
Why is the onset of TAO not always synchronous with the development of hyperthyroidism?
Onset of TAO can precede, follow, or may occur concurrently with hyperthyroidism in patients with Graves’ disease. Therefore, TAO and hyperthyroidism were considered as different diseases in the past. However, patients with euthyroid TAO often have subtle thyroid function abnormalities, and there is a qualitative correlation between the presence of TRAbs and the occurrence of TAO and thyrotoxicosis. Hence, it has been reconciled that both TAO and hyperthyroidism are a spectrum of the same autoimmune thyroid disease. Differential responsiveness of orbital fibroblast
63
What imaging features are consistent with the diagnosis of TAO?
Imaging features consistent with the diagnosis of TAO include extraocular muscle belly thickening with tendon sparing.
64
When is surgery indicated in patients with TAO?
Surgery is indicated only in patients with dysthyroid optic neuropathy, corneal breakdown, and globe subluxation who do not respond to glucocorticoids within 1-2 weeks.
65
What is the recommended duration of consistent inactivity of eye disease before rehabilitative surgeries are undertaken?
Rehabilitative surgeries are undertaken once the eye disease is consistently inactive for 6 months.
66
What are the criteria for using the turbo PTH assay?
The criteria for using the turbo PTH assay are young (<30 years), non-localization of an abnormal gland, and parathyroid malignancy.
67
How does the turbo PTH assay provide faster results compared to conventional assays?
The turbo PTH assay provides faster results by increasing the incubation temperature from 20°C to 45°C and shaking speed from 180 to 400 rpm, reducing the incubation time to 7 minutes instead of 1-2 hours.
68
What is the Miami criterion used for in parathyroidectomy?
The Miami criterion is used to define the success of parathyroidectomy. It requires a >50% reduction in serum PTH levels 10 minutes after excision of the suspected abnormal gland, compared to the highest pre-incision or pre-excision serum PTH level.
69
What is the accuracy of intraoperative PTH (IOPTH) in predicting cure for solitary adenoma and multiglandular disease?
The accuracy of IOPTH in predicting cure for solitary adenoma is 97%, while for multiglandular disease it is 58%.
70
What are the biochemical alterations that occur after parathyroid surgery?
After successful removal of an abnormal parathyroid gland, PTH levels decline by >50% intraoperatively and return to the reference range within 30 hours. Serum calcium decreases by 12 hours and reaches a nadir by 24-36 hours postoperatively. Serum phosphate may normalize or decline, depending on the severity of preexisting bone disease.
71
What is the effect of curative parathyroidectomy on bone mineral density (BMD)?
Curative parathyroidectomy results in a significant increase in BMD at the spine and hip, increasing by approximately 5-10% in the first year and continuing to increase by 12-15% over ten years. However, there is minimal or no change in BMD at the distal radius, which is predominantly composed of cortical bone.
72
What are the causes of hypocalcemia after parathyroidectomy?
Hypocalcemia after parathyroidectomy can occur due to hungry bone syndrome, transient hypoparathyroidism, hypomagnesemia, and permanent hypoparathyroidism. Hungry bone syndrome is the most common cause in patients with symptomatic primary hyperparathyroidism (PHPT).
73
What is hungry bone syndrome and how is it characterized?
Hungry bone syndrome (HBS) is characterized by the 'increased appetite of bone' for calcium and phosphorus, resulting from a sudden decrease in osteoclastic activity combined with continued osteoblast activity. Biochemically, it is characterized by hypocalcemia, hypophosphatemia, hypomagnesemia, raised alkaline phosphatase, and hypocalciuria.
74
What is diabetic embryopathy?
Diabetic embryopathy is a result of peri-conceptional uncontrolled hyperglycemia which influences organogenesis during the embryonic period.
75
What are some congenital anomalies associated with diabetic embryopathy?
The congenital anomalies associated with diabetic embryopathy include neural tube defects, caudal regression syndrome, transposition of great vessels, ventricular septal defect, hypoplastic left heart syndrome, renal agenesis, duodenal atresia, and hypoplastic femur.
76
What is the diabetes-specific defect in diabetic embryopathy?
The diabetes-specific defect in diabetic embryopathy is caudal regression syndrome (sacral agenesis).
77
What are the maternal risks associated with GDM?
Women with GDM have an increased risk of preeclampsia, fetal loss, difficult labor, and future risk of developing T2DM.
78
What are the immediate risks to the fetus associated with GDM?
The immediate risks to the fetus associated with GDM include macrosomia (>4 kg), intrauterine death (if FPG >105 mg/dl), neonatal hypoglycemia, polycythemia, hypocalcemia, and hyperbilirubinemia.
79
When should hyperglycemia screening be done in pregnancy?
Hyperglycemia screening should be done in every pregnant woman as early as possible (first contact visit or preferably <12 weeks) to avoid missing preexisting diabetes. Retesting is also recommended in all women between 24 and 28 weeks of gestation.
80
Who should be screened for hyperglycemia in the first trimester of pregnancy?
According to ADA guidelines, individuals with a high risk of having type 2 diabetes require screening at the first trimester of pregnancy. Therefore, all adult women with a prepregnant BMI >25 kg/m2 with one additional risk factor like hypertension or polycystic ovarian disease, ethnic group with high diabetes prevalence, the presence of family history of diabetes in the first-degree relatives, or personal history of abnormal glucose intolerance or bad obstetric outcome should be screened for hyperglycemia in the first trimester.
81
Who should be screened for hyperglycemia at 24–28 weeks of gestation?
All pregnant women require screening for hyperglycemia with an oral glucose challenge test at 24–28 weeks of gestation, except those who were diagnosed with overt diabetes (FPG ≥126 mg/dl, RPG ≥200 mg/dl, or HbA1c ≥6.5%) in the first trimester.
82
What are the emergencies in a patient with acromegaly?
Patients with acromegaly can present in emergency due to pituitary apoplexy, subarachnoid hemorrhage, status epilepticus, paraplegia, accelerated hypertension, diabetic ketoacidosis, gastrointestinal bleed, cardiac arrhythmias, and acromegalic cardiomyopathy.
83
What are the unusual signs in patients with acromegaly?
The unusual signs in patients with acromegaly include cutis verticis gyrata, facial asymmetry, tonsillomegaly, acromegalic rosary, orchidomegaly, gynecomastia, osteoma, and tarsal tunnel syndrome.
84
What are the causes of cutis verticis gyrata?
Cutis verticis gyrata is not a specific feature of acromegaly, but is also seen in patients with neurofibroma, pachydermoperiostitis, melanocytic nevi, myxedema, and amyloidosis.
85
What are the causes of headache in acromegaly?
Headache in acromegaly can be caused by increased intrasellar pressure in microadenomas, stretching of the dura in macroadenomas, calvarial thickening, osteomas, recurrent sinusitis, and secretion of putative algesic peptides by the tumor tissue.
86
What are the causes of macroglossia?
Causes of macroglossia include acromegaly, primary hypothyroidism, Down's syndrome, amyloidosis, hemangioma, lymphangioma, and tongue neoplasms.
87
What are the oral manifestations of acromegaly?
Oral manifestations in a patient with acromegaly include prognathism, thick fleshy lips, increased spacing between teeth, malalignment of jaw, macroglossia, and tonsillomegaly.
88
What are the cutaneous manifestations of acromegaly?
The cutaneous manifestations in a patient with acromegaly include hyperhidrosis, seborrhea, hirsutism, acanthosis nigricans, skin tags, hyperpigmentation, and cutis verticis gyrata.
89
Why are hands warm and moist in patients with acromegaly?
GH promotes peripheral deiodinase activity and increases T4 to T3 neogenesis, which is responsible for the increased adrenergic sensitivity manifesting clinically as warm and moist hands. The direct effect of GH on sweat glands also contributes.
90
What are the causes of abdominal pain and vomiting in a patient with diabetes?
Abdominal pain and vomiting can occur in a patient with diabetes due to diabetic ketoacidosis, acute pancreatitis, acute cholecystitis, acute papillary necrosis, gastroparesis, and diabetic kidney disease. Drugs like metformin, gliptins, and GLP1 analogues may also cause abdominal pain, nausea, and vomiting in these patients.
91
What can mimic acute abdomen in a patient with diabetes?
Acute coronary syndrome may mimic acute abdomen in a patient with diabetes.
92
What are the potential causes of anemia in patients with Type 1 Diabetes Mellitus?
Patients with Type 1 Diabetes Mellitus are predisposed to various causes of anemia such as celiac disease, pernicious anemia, and autoimmune thyroid disorders.
93
What is the definition of gestational diabetes mellitus?
Gestational diabetes mellitus (GDM) is defined as glucose intolerance of any severity with onset or first recognition during pregnancy.
94
What are the limitations of the definition of GDM?
The definition of GDM, which entails glucose intolerance of any severity and first recognition during pregnancy, has limitations. It categorizes all women with hyperglycemia as GDM, even though hyperglycemia due to pregnancy is milder than hyperglycemia associated with preexisting diabetes. The differentiation between preexisting diabetes and hyperglycemia during pregnancy is important for monitoring and managing complications. Additionally, the definition does not consider the absolute numerical values of plasma glucose to define hyperglycemia during pregnancy.
95
What are the differences between a patient with preexisting diabetes and gestational diabetes?
Patients with preexisting diabetes have diabetes onset before conception, while gestational diabetes occurs after conception. Preexisting diabetes can be Type 2 Diabetes Mellitus or Type 1 Diabetes Mellitus, whereas gestational diabetes is characterized by transient hyperglycemia. Diabetic complications, such as microangiopathy and macroangiopathy, are more common in preexisting diabetes. Maternal and neonatal risks differ between the two conditions.
96
What is fuel-mediated teratogenesis?
Fuel-mediated teratogenesis refers to teratopathy occurring due to exposure of the embryo or fetus to high levels of glucose and ketones during pregnancy with diabetes. The type and severity of defects depend on the timing of exposure, with diabetic embryopathy occurring during embryogenesis and anthropometric and metabolic abnormalities occurring if the fetus is exposed to the abnormal metabolic milieu after 8 weeks of gestation.
97
What is the appropriate term for hyperglycemia during pregnancy instead of GDM?
The appropriate term for hyperglycemia during pregnancy is 'hyperglycemia during pregnancy' rather than GDM.
98
What is the role of bisphosphonates in the perioperative period?
Bisphosphonates should be administered, if indicated, in the perioperative period.
99
Why should incentive spirometry be advised in the perioperative period?
Incentive spirometry should be advised to reduce postoperative morbidity.
100
How should patients with Cushing's disease be handled during shifting?
Gentle handling of the patient should be ensured during shifting to avoid fragility fracture.
101
Why should glucocorticoid not be administered preoperatively in patients with Cushing's disease?
Glucocorticoid should not be administered preoperatively in patients with Cushing's disease because it may interfere with postoperative monitoring of cortisol and may increase morbidity by exacerbating preexisting hypercortisolemia.
102
What is the prior medical therapy indicated for patients who are moribund and at high risk for surgery?
Prior medical therapy with ketoconazole/metyrapone/pasireotide is indicated in those who are moribund and are at high risk for surgery, to achieve rapid eucortisolemia.
103
Why are patients with Cushing's syndrome predisposed to thromboembolic diseases?
Patients with Cushing's syndrome are predisposed to thromboembolic diseases due to cortisol excess, which is associated with a procoagulant state.
104
What are the predictors of cure in Cushing's disease?
The predictors of cure in Cushing's disease are well-localized microadenoma without parasellar extension, postoperative 0800h cortisol between day 1 and 7 < 50 nmol/L (1.8 μg/dl), plasma ACTH <20 pg/ml within 24 h of surgery, histological documentation of pituitary adenoma, positive ACTH immunostaining, and prolonged requirement of glucocorticoid replacement.
105
Are remission and cure synonymous in Cushing's disease?
No, remission and cure are not synonymous in Cushing's disease. Remission refers to the resolution of signs and symptoms, while cure additionally requires restoration of diurnal rhythm of cortisol secretion, normalization of urine free cortisol (UFC), suppressibility of cortisol after overnight dexamethasone suppression test (ONDST), and stimulability with 250 μg/1 μg ACTH without the need for glucocorticoid replacement and no evidence of other pituitary hormone deficiencies.
106
What is the relationship between overt hypercalcemia and vitamin D deficiency in patients with PHPT?
Overt hypercalcemia occurs in patients of PHPT with concurrent vitamin D deficiency.
107
In patients with secondary hyperparathyroidism due to vitamin D deficiency, what happens to the PTH levels?
The PTH levels decrease/normalize without the development of hypercalcemia.
108
List the familial causes of PTH-dependent hypercalcemia.
The familial causes of PTH-dependent hypercalcemia are multiple endocrine neoplasia (MEN1, MEN2a, and MEN4), familial hypocalciuric hypercalcemia, neonatal severe hyperparathyroidism, hyperparathyroidism–jaw tumor syndrome, and familial isolated hyperparathyroidism.
109
What percentage of PTH-dependent hypercalcemia is contributed by familial causes?
Familial causes contribute to only 5% of PTH-dependent hypercalcemia.
110
What is the most common endocrine manifestation in patients with multiple endocrine neoplasia type 1 (MEN1)?
The most common endocrine manifestation in patients with MEN1 is primary hyperparathyroidism (PHPT).
111
What is the difference between PHPT in patients with MEN1 and sporadic PHPT?
PHPT in patients with MEN1 has an earlier age of onset (20-25 years), equal male-to-female ratio, phenotypic markers like facial angiofibromas, collagenomas, and a higher risk for hypoparathyroidism. Sporadic PHPT usually occurs after the age of 50, has a higher prevalence in females, no phenotypic markers, and a low risk for hypoparathyroidism.
112
When is surgery recommended for patients with PHPT and MEN1?
Surgery is recommended for symptomatic patients with PHPT and MEN1. Bilateral neck exploration is the preferred approach due to multiglandular involvement, and 3.5 gland excision is recommended.
113
What is hyperparathyroidism-jaw tumor syndrome (HPT-JT)?
Hyperparathyroidism-jaw tumor syndrome is an autosomal dominant disorder characterized by fibro-osseous tumors of the mandible and/or maxilla with primary hyperparathyroidism. It is associated with ossifying fibromas of the jaw, multiglandular involvement with cystic adenomas, and has a potential risk for malignancy.
114
How is a mass localized in the left suprarenal region?
A SPECT/CT fusion image can localize the mass to the left suprarenal region.
115
What is the preferred choice for further investigation if the CT abdomen fails to localize the catecholamine-secreting tumor?
The preferred choice is a 123I-MIBG scan, which has a sensitivity of 80-90% to localize the source of catecholamine excess.
116
What are the causes of false-negative 123I-MIBG scan?
The causes of false-negative 123I-MIBG scan are metastatic pheochromocytoma, paraganglioma (especially SDHB related), and necrotic tumors. Certain drugs like calcium channel blockers, labetalol, tricyclic antidepressants, and sympathomimetics can also interfere with 123I-MIBG uptake and cause a false-negative scan.
117
What is the recommended preoperative management for pheochromocytoma/paraganglioma?
Preoperative management should focus on controlling blood pressure and appropriate volume expansion. Nonselective α-blocker, phenoxybenzamine, or selective α-1 blocker, prazosin, are used for preoperative α-blockade. After achieving adequate α-blockade, salt ad lib and β-blockers should be added. Calcium channel blockers may be required if blood pressure is not controlled with α-blockers and β-blockers. The target blood pressure prior to surgery is <130/80 mmHg (seated) and systolic blood pressure >90 mmHg on standing.
118
In which disorders is salt ad lib recommended despite the presence of hypertension?
Salt ad lib is advocated in patients with pheochromocytoma and primary aldosteronism, regardless of the presence of hypertension. In pheochromocytoma, salt ad lib diet is required to replete the intravascular volume. In primary aldosteronism, salt ad lib improves the sensitivity of the screening test and helps identify hypokalemia.
119
What are the preferred anesthetic agents in pheochromocytoma/paraganglioma?
Propofol, etomidate, or barbiturates in combination with synthetic opioids are preferred as anesthetic agents in pheochromocytoma/paraganglioma.
120
What are the typical locations where phosphaturic mesenchymal tumors are commonly found?
Phosphaturic mesenchymal tumors are commonly located in extremities and paranasal sinuses.
121
What is the histological grouping of phosphaturic mesenchymal tumors?
Phosphaturic mesenchymal tumors are grouped as 'phosphaturic mesenchymal tumors - mixed connective tissue variant (PMT-MCT)' and include hemangiopericytomas, hemangioma, sarcoma, ossifying fibroma, and rarely osteoblastoma.
122
What percentage of phosphaturic mesenchymal tumors are benign?
Approximately 90% of phosphaturic mesenchymal tumors are benign.
123
What are the clinical clues to suspect tumor-induced osteomalacia?
Clinical clues to suspect tumor-induced osteomalacia include osteomalacia with normocalcemia, severe hypophosphatemia, normal or mildly elevated alkaline phosphatase, normal PTH and 25(OH) D levels, failure to respond to cholecalciferol/calcitriol, and worsening of hypophosphatemia after rPTH therapy initiated for osteoporosis management.
124
Which phosphatonin is clinically most relevant in tumor-induced osteomalacia (TIO)?
FGF23 is the clinically most relevant phosphatonin in tumor-induced osteomalacia (TIO).
125
What is the hallmark biochemical abnormality in tumor-induced osteomalacia?
The hallmark biochemical abnormality in tumor-induced osteomalacia is severe hypophosphatemia due to renal phosphate wasting caused by the secretion of FGF23 from mesenchymal tumors.
126
What is the preferred functional imaging for localizing tumors in patients with tumor-induced osteomalacia (TIO)?
Octreotide-based scintigraphy (e.g., 68Ga-DOTATATE PET-CT) is the preferred functional imaging for localizing tumors in patients with tumor-induced osteomalacia (TIO).
127
Why is octreotide-based scintigraphy preferred over 18F-FDG-PET for tumor localization in TIO?
Octreotide-based scintigraphy is more sensitive and specific than 18F-FDG-PET scan for the localization of tumor in tumor-induced osteomalacia (TIO) due to the low proliferative indices of these tumors and FDG uptake by metabolically active fracture sites.
128
What are the surrogate laboratory evidences for primary aldosteronism?
The surrogate laboratory evidences for primary aldosteronism are hypokalemia, metabolic alkalosis, hypomagnesemia, mild hypernatremia, hyperglycemia, proteinuria, U waves in ECG, and left ventricular hypertrophy.
129
What are the biochemical abnormalities associated with primary aldosteronism?
The biochemical abnormalities associated with primary aldosteronism are hypokalemia, metabolic alkalosis, hypomagnesemia, mild hypernatremia, hyperglycemia, and proteinuria.
130
What are the causes of hypokalemia in primary aldosteronism?
The causes of hypokalemia in primary aldosteronism are increased cellular exchange with sodium and potassium wasting.
131
What causes metabolic alkalosis in primary aldosteronism?
Metabolic alkalosis in primary aldosteronism is caused by loss of H+ into urine, shift of H+ into potassium-depleted cells, and increased bicarbonate reabsorption.
132
What leads to hypomagnesemia in primary aldosteronism?
Hypomagnesemia in primary aldosteronism is caused by increased tubular secretion of magnesium.
133
What is the effect of aldosterone on sodium reabsorption?
Aldosterone increases sodium reabsorption, leading to mild hypernatremia in primary aldosteronism.
134
What are the precautions required prior to investigation in a patient with primary aldosteronism?
Prior to investigation, precautions include selecting appropriate antihypertensives, salt ad lib, normalizing serum potassium, and ensuring adequate measures for blood sampling.
135
Which antihypertensive drugs are preferred in patients with primary aldosteronism?
The preferred antihypertensive drugs are prazosin and verapamil as they do not interfere with the renin-angiotensin-aldosterone system (RAAS).
136
What are the target glucose levels for fasting and post-meal in women with gestational diabetes mellitus (GDM)?
The target glucose levels for fasting is 90–130 mg/dl and for post-meal is <180 mg/dl.
137
What should be done with glucose-lowering therapy (insulin/OADs) immediately after delivery in patients with GDM?
Glucose-lowering therapy should be discontinued immediately after delivery in patients with GDM.
138
How long should blood glucose (fasting and postprandial) be monitored after delivery in women with GDM?
Blood glucose should be monitored for 24-72 hours after delivery in women with GDM.
139
What should be done at 6-12 weeks postpartum in women who had GDM?
Women who had GDM should be subjected to a 75-g OGTT to categorize them as normal, prediabetes, or diabetes using the standard criteria for nonpregnant adults.
140
What is the suggested treatment option to manage diabetes during lactation?
The best treatment option is possibly insulin. However, metformin and second-generation sulfonylureas (glibenclamide and glipizide) have been safely used in lactating women.
141
What is the concentration of metformin in breast milk and its effect on infants?
Metformin is secreted into breast milk in the range of 0.28-1.08%, but this concentration is too low to have any detrimental effects on the infant. The use of metformin had no adverse effect on infant growth and motor and social development during the first 6 months of life.
142
Which antidiabetic medications are extensively bound to circulating proteins and not secreted into breast milk?
Glibenclamide and glipizide are extensively bound to circulating proteins and hence not secreted into breast milk.
143
Is there data available regarding the use of glimepiride or gliclazide during lactation?
No, there is no data available regarding the use of glimepiride or gliclazide during lactation.
144
What is the suggested reading for Acromegaly: Diagnosis and Treatment?
Suggested Reading. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 37
145
What is the clinical round mentioned in the notes for Acromegaly?
Clinical Rounds. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21
146
What is the suggested reading for Hyperprolactinemia?
Suggested Reading. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 66
147
What is the case vignette mentioned in the notes for Hyperprolactinemia?
Case Vignette . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 39
148
What is the stepwise analysis mentioned in the notes for Hyperprolactinemia?
Stepwise Analysis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 40
149
What is the clinical round mentioned in the notes for Hyperprolactinemia?
Clinical Rounds . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 41
150
What is the suggested reading for Cushing's Syndrome: Clinical Perspectives?
Suggested Reading . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 94
151
What is the case vignette mentioned in the notes for Cushing's Syndrome: Clinical Perspectives?
Case Vignette . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 67
152
What are the illicit stimulators in ACTH-independent macronodular adrenal hyperplasia?
The illicit stimulators in ACTH-independent macronodular adrenal hyperplasia include arginine vasopressin, glucose-dependent insulinotropic peptide, beta-adrenergic agonist, LH/hCG, serotonin, leptin, and angiotensin II.
153
What is the exact pathogenesis of ACTH-independent macronodular adrenal hyperplasia (AIMAH)?
The exact pathogenesis of ACTH-independent macronodular adrenal hyperplasia is not known, but it is believed to be a result of overexpression or ectopic expression of receptors for peptide hormones/amines on adrenocortical cells.
154
What has been reported to cause ACTH-independent macronodular adrenal hyperplasia?
Mutations of a putative tumor suppressor gene, armadillo repeat containing 5 (ARMC5), have been reported to cause ACTH-independent macronodular adrenal hyperplasia.
155
What are the alterations in cortisol dynamics during pregnancy?
During pregnancy, cortisol levels are high, dexamethasone test is non-suppressible, and UFC (urine free cortisol) and ACTH levels are mildly elevated. The circadian rhythm of cortisol secretion is preserved, with higher levels overall.
156
When should Cushing's syndrome be suspected in pregnancy?
Cushing's syndrome should be suspected in pregnancy when distinctive features such as proximal myopathy, maternal weight gain with fetal intrauterine growth retardation, worsening of glycemic control, and hypertension are present.
157
How is the diagnosis of Cushing's syndrome in pregnancy established?
The diagnosis of Cushing's syndrome in pregnancy is established by measuring urine free cortisol (UFC). A UFC value more than three times the upper limit of normal is diagnostic of Cushing's syndrome.
158
What is the common cause of Cushing's syndrome during pregnancy?
The common cause of Cushing's syndrome during pregnancy is adrenal adenoma, followed by Cushing's disease. Even in patients with adrenal adenoma, plasma ACTH levels are measurable due to the stimulatory effect of placental CRH on the maternal HPA axis.
159
What is an adrenal incidentaloma?
An adrenal incidentaloma is an adrenal mass larger than 1 cm that is incidentally detected on imaging during evaluation for a reason unrelated to adrenal disorder, excluding those detected during cancer staging.
160
What is persistent or recurrent PHPT?
Persistent PHPT is defined as hypercalcemia that either persists or recurs within 6 months of parathyroid surgery. Reappearance of hypercalcemia after 6 months of curative parathyroid surgery is termed as recurrent PHPT.
161
What are the causes of persistent/recurrent PHPT?
The causes of persistent/recurrent PHPT include failure to localize abnormal parathyroid gland intraoperatively, incomplete excision of adenoma, multiglandular disease (familial syndromes), ectopic parathyroid adenoma, and rarely parathyroid carcinoma.
162
What is the role of preoperative imaging in patients with recurrent/persistent PHPT?
Preoperative localization is mandatory prior to any surgical intervention. USG neck and 99mTc-sestamibi-SPECT scintigraphy are recommended as the initial imaging modalities. If the results are concordant, accuracy of this combined approach is 90%, and no further investigation is required.
163
Which imaging modalities are helpful in localizing ectopic lesion in the mediastinum?
CT and MRI are helpful in localizing ectopic lesion in the mediastinum with a sensitivity of 46–87%.
164
What is the sensitivity of USG-guided FNAC in the diagnosis of parathyroid lesion?
USG-guided FNAC of suspected lesion with assessment of tissue PTH level has a sensitivity of 87% in the diagnosis of parathyroid lesion.
165
When should patients with recurrent/persistent PHPT be treated surgically?
Indications for surgery are essentially the same as in surgically naive patients. All symptomatic patients should be subjected to surgery. Those with non-localization or discordant results on USG and MIBI should undergo further imaging, and failure to localize warrants bilateral neck exploration.
166
What is the surgical cure rate in patients with recurrent/persistent PHPT?
Surgical cure rate is 85–90% in patients with recurrent/persistent disease as compared to 95–97% in surgically naive patients.
167
Why should asymptomatic patients with recurrent/persistent hyperparathyroidism be kept under regular surveillance?
Patients with recurrent/persistent hyperparathyroidism who are asymptomatic or who have mild disease should be kept under regular surveillance. This is because of difficulties associated with redo surgery due to distorted neck anatomy, higher risk of recurrent laryngeal nerve injury, and hypocalcemia.
168
Who should be screened for osteoporosis?
Screening for osteoporosis is recommended in individuals who have a high risk for fragility fracture. The indications as recommended by the National Osteoporosis Foundation are summarized in the table given below.
169
What are the indications for BMD measurement in osteoporosis screening?
The indications for BMD measurement in osteoporosis screening are: all women ≥65 years or men ≥70 years, younger postmenopausal women, perimenopausal women, and men aged 50–69 with clinical risk factors for fracture, and adults with fracture after the age >50 years or disorders and/or drugs associated with osteoporosis.
170
Why is there a need for a fracture prediction tool?
The occurrence of fragility fracture is not solely dependent on decreased bone mineral density, but is rather a culmination of multiple risk factors. Hence, there is a need to devise a comprehensive tool to precisely predict the fracture risk in an individual.
171
What are some important risk factors for fragility fracture?
Some important risk factors for fragility fracture include advanced age, female sex, low body weight, past/family history of fracture, visual impairment, neuromuscular dysfunction, smoking, alcohol, and use of glucocorticoids.
172
What is the FRAX score used for?
The FRAX score is a web-based algorithm designed to calculate the 10-year probability of a major osteoporosis-related fracture or hip fractures alone. It is applicable for both men and women.
173
What are the risk factors used for fracture prediction in the FRAX score?
The risk factors used for fracture prediction in the FRAX score include body weight, previous history of fracture, history of hip fracture in parents, current smoking, use of glucocorticoids, rheumatoid arthritis, alcohol use, and secondary osteoporosis.
174
What are the advantages of the FRAX score?
The advantages of the FRAX score include being inexpensive, convenient, easy to use, and comprehensive. It also takes into account the effect of race and ethnicity for the assessment of fracture risk.
175
What are the limitations of the FRAX score?
The limitations of the FRAX score include not considering independent risk factors like number of falls, visual impairment, neuromuscular dysfunction, vitamin D deficiency, and physical inactivity. It also cannot assess fracture risk in individuals aged <40 or >90 years and is not validated for monitoring therapeutic response.
176
What are some causes of bilateral pheochromocytoma?
The causes of bilateral pheochromocytoma are MEN2A, MEN2B, von Hippel–Lindau disease, and familial paraganglioma syndrome like SDHB and SDHD mutations.
177
Do bilateral pheochromocytomas occur in all familial syndromes?
No, some familial syndromes like NF1-related pheochromocytoma are usually unilateral and not associated with bilateral pheochromocytoma.
178
What is the hormone secretory pattern of pheochromocytomas?
Catecholamine-secreting tumors originating from the adrenal gland can secrete both epinephrine and norepinephrine.
179
Can functional paragangliomas secrete epinephrine?
No, functional paragangliomas can only secrete norepinephrine. They lack the enzyme PNMT required for the conversion of norepinephrine to epinephrine.
180
What are the characteristic features of pheochromocytoma associated with multiple endocrine neoplasia type 2 (MEN2)?
MEN2-related pheochromocytomas are always adrenal, predominantly secrete epinephrine, and are almost never malignant.
181
What is von Hippel–Lindau disease?
Von Hippel–Lindau disease is an autosomal dominant disorder characterized by bilateral pheochromocytoma and/or paraganglioma, nonfunctioning pancreatic islet cell tumor, hemangioblastomas of cerebellum, brainstem or spinal cord, retinal angiomas, and clear cell renal cell carcinoma.
182
Why does pheochromocytoma associated with VHL predominantly produce norepinephrine?
Patients with VHL having bilateral pheochromocytomas predominantly produce norepinephrine due to the under-expression of the enzyme PNMT.
183
What are the characteristics of TMEM127 and MAX mutation-associated PPGL?
TMEM127 and MAX mutation-related catecholamine-secreting tumors are familial in origin, present at a later age (40–50 years), and have mutations in the TMEM127 and MAX genes.
184
What are the potential causes of the increase in the incidence of T1DM?
The increase in the incidence of T1DM may be partially attributed to the hygiene hypothesis and the accelerator hypothesis.
185
What is the hygiene hypothesis?
The hygiene hypothesis proposes that improvements in living conditions result in a lack of early exposure to pathogens, leading to inadequate maturation of the immune system and increased predisposition to autoimmune disorders, including T1DM.
186
What is the accelerator hypothesis?
The accelerator hypothesis suggests that there is an enhanced immuno-inflammatory destruction of β-cells in response to increased insulin resistance associated with obesity.
187
Which HLA loci are protective for T1DM?
The HLA loci DRB1*1501, DQA1*0102, DQ6, and DRB1*1401 are protective for T1DM, although their presence may not confer protection in all cases.
188
How does obesity predispose to T1DM?
Obesity increases the risk of developing T1DM by accelerating the immuno-inflammatory destruction of β-cells through insulin resistance and the release of adipocytokines (IL6 and TNFα).
189
What is the term used to describe the combination of type 1 diabetes with insulin resistance?
The combination of type 1 diabetes with insulin resistance is known as 'double diabetes'.
190
What are some animal models of T1DM?
Some animal models of T1DM include the Nonobese diabetic (NOD) mouse, BioBreeding (BB) rat, Long–Evans Tokushima Lean (LETL) rat (spontaneous models), and streptozotocin- or alloxan-induced diabetic Wistar rat (induced models).
191
What is a 'pseudoatrophic' islet?
In patients with long-standing T1DM, the selective destruction of β-cells eventually leads to the disappearance of β-cells and the infiltrates, leaving behind clumps of islet containing α-cells, which are termed as 'pseudoatrophic' islets.
192
What are the distinctive features of T1DM?
The distinctive features of T1DM are young age of onset, absolute insulin deficiency, and presence of islet autoimmunity.
193
What are the causes of PHPT?
A single parathyroid adenoma accounts for approximately 80–85% of patients with PHPT, and double adenomas are found in 4–5%. Multiple gland hyperplasia contributes to approximately 10% of patients with PHPT, while parathyroid carcinoma is rare (<1%).
194
Is there any correlation between clinical phenotype and histology of parathyroid adenoma in patients with PHPT?
Most parathyroid adenomas or hyperplasia arise from chief cells. Rarely (3%) adenomas can arise from oxyphil cells which are usually larger than chief cell adenomas and have modestly elevated PTH. Clear cell adenomas are rare with anecdotal case reports.
195
Why is PHPT a disease of postmenopausal women?
Postmenopausal state is characterized by estrogen deficiency. Estrogen inhibits the action of PTH by interfering with post-receptor signaling (cAMP-dependent protein kinase) and antagonizes cytokine-mediated bone resorption. Hence, estrogen deficiency in postmenopausal state leads to unopposed PTH action, thereby unmasking PHPT. In addition, estrogen deficiency may have a role in parathyroid tumorigenesis.
196
What are the mechanisms implicated in parathyroid tumorigenesis?
The exact pathogenesis of parathyroid tumorigenesis is still elusive, but it seems to be multifactorial in origin, except in familial syndromes where exact mutation can be detected. Sporadic PHPT accounts for 95% of patients and harbors single or double adenoma, while the rest are contributed by familial syndromes and usually have parathyroid hyperplasia.
197
Why is inferior parathyroid gland more likely to be ectopic?
Parathyroid glands are endodermal in origin and develop from the pharyngeal pouch. Superior parathyroid glands originate from the fourth pharyngeal pouch, while inferior parathyroid glands from the third pharyngeal pouch. Because inferior parathyroid glands have to travel a longer distance as compared to superior parathyroid glands, they are more likely to be ectopic in location.
198
Why is there a differential effect of parathyroid hormone on cortical and cancellous bone?
The skeletal tissue is composed of cortical and cancellous bone in varying proportions. PTH has an anabolic effect on cancellous bone and resorptive effect on cortical bone.
199
What is the preferred insulin for CSII therapy?
The preferred insulin for CSII therapy is regular or rapid-acting analogues.
200
Why are rapid-acting analogues preferred for CSII therapy?
Rapid-acting analogues are preferred for CSII therapy because they are monomeric and have a favorable pharmacokinetic profile, resulting in better glycemic control.
201
What are the three types of insulin pumps available for delivery of insulin through CSII?
The three types of insulin pumps available for delivery of insulin through CSII are earlier models without integrated continuous glucose monitoring system (CGMS), next-generation pumps integrated with CGMS, and current generation pumps with provision for suspending insulin delivery in the event of hypoglycemia.
202
What is the difference between 'open-loop' and 'closed-loop' insulin pumps?
An 'open-loop' insulin pump delivers insulin at a preset rate and requires manual adjustment, while a 'closed-loop' insulin pump has a provision for automated adjustment in the rate of insulin delivery depending on the ambient blood glucose level.
203
Which non-insulin therapies have been explored in the management of patients with T1DM?
Non-insulin therapies explored in the management of patients with T1DM include metformin, pioglitazone, α-glucosidase inhibitors, dipeptidyl peptidase-4 (DPP4) inhibitors, glucagon-like peptide-1 (GLP-1) analogues, and pramlintide.
204
What is the mechanism of action of DPP4 inhibitors/GLP-1 analogues in T1DM?
The mechanism of action of DPP4 inhibitors/GLP-1 analogues in T1DM is to decrease glucagon secretion from α-cells and to delay intestinal absorption of glucose.
205
How does GLP-1 inhibit glucagon?
GLP-1 inhibits glucagon by direct inhibition of α-cells, restoration of 'glucose–glucagon axis,' and increased somatostatin secretion.
206
What is the Edmonton protocol?
The Edmonton protocol is a steroid-sparing immunosuppressive protocol used in patients with T1DM who undergo islet transplantation. It includes administration of sirolimus, tacrolimus, and daclizumab, thereby avoiding the adverse effects associated with the use of glucocorticoids.
207
What can competitively inhibit NIS and interfere with the transport of iodine into follicular cells?
Fluoride, thiocyanate, perchlorate, and nitrate.
208
What are the clinical and biochemical profiles for subacute thyroiditis and diffuse toxic goiter due to Graves' disease?
Rapid weight loss, tremor, tachycardia, elevated T3 and T4, suppressed TSH, and grade I diffuse goiter.
209
What is the best investigation to differentiate between subacute thyroiditis and diffuse toxic goiter due to Graves' disease?
A thyroid uptake study.
210
What will be the thyroid uptake in thyroiditis and Graves' disease?
Thyroid uptake will be low or suppressed in thyroiditis, while it will be high in Graves' disease.
211
What are the available treatment modalities for hyperthyroidism?
Antithyroid drugs (ATD), 131I radio-ablation, and thyroid surgery.
212
What are the three available antithyroid drugs and their summarized properties?
Carbimazole (oral bioavailability: 93%, protein binding: nil, half-life: 6-8 h), Methimazole (oral bioavailability: 93%, protein binding: nil, half-life: 6-8 h), and Propylthiouracil (PTU) (oral bioavailability: 65-75%, protein binding: 75%, half-life: 1-2 h).
213
Why are carbimazole and methimazole preferred antithyroid drugs in the management of Graves' disease?
They have once daily dosing, achieve euthyroid state earlier, have a longer intra-thyroidal half-life, and fewer side effects compared to PTU.
214
When is propylthiouracil (PTU) preferred in the treatment of hyperthyroidism?
It is preferred during the first trimester of pregnancy due to its low transplacental passage, and in patients with thyroid storm as it inhibits peripheral T4 to T3 conversion.
215
How does insulin degludec differ from glargine?
Insulin degludec differs from glargine in that it has an ultra long duration of action of nearly 40 h, is truly peakless, has a neutral pH, flexibility of administration during anytime of the day between 8 and 40 h, and can be mixed with other insulins.
216
Why is insulin degludec long acting?
Insulin degludec is long acting because it is modified with deletion of the last amino acid from the B-chain and addition of hexadecanedioic fatty acid at the 29th position. This modification creates dihexamers in the presence of phenol and zinc, which prolongs the resident time of insulin in subcutaneous tissue.
217
What are the advantages of using premixed insulin therapy in the management of T2DM?
Premixed insulin therapy reduces the number of injections and increases patient's convenience by providing both basal and pre-prandial insulin as a single injection. It is useful in patients with both fasting and post-prandial hyperglycemia, particularly in those with some residual endogenous β-cell reserve.
218
When should insulin be initiated in patients with type 2 diabetes at diagnosis?
Insulin should be initiated at diagnosis in patients with type 2 diabetes who have HbA1c >9%, osmotic symptoms, significant weight loss, fasting plasma glucose >200–250 mg/dl, ketosis/ketoacidosis, and in the presence of complications like infections and acute coronary syndrome, as well as significant hepatic or renal dysfunction.
219
What is Monnier's hypothesis?
Monnier's hypothesis dissects the contribution of fasting and postprandial hyperglycemia at different levels of HbA1C. At an HbA1C <7.3%, approximately 70% of the glycemic burden is contributed by post-prandial hyperglycemia, and the rest by fasting hyperglycemia.
220
What should be targeted first in a patient with diabetes who has both fasting and postprandial hyperglycemia?
In a patient with T2DM who has both fasting and post-prandial hyperglycemia, the HbA1c is likely to be >8%. At this level of glycemia, the contribution of fasting hyperglycemia is approximately 50% to the overall glycemic burden, and it progressively increases.
221
Why may TSH remain suppressed for a longer duration in patients with hyperthyroidism on treatment?
TSH may remain suppressed for a longer duration in patients with hyperthyroidism on treatment due to the prolonged inhibitory effect of circulating T3 and T4 on thyrotropes, as well as the suppressive effect of intrapituitary cytokines (TNF-α and IL-6 released by pituicytes).
222
What is the recommended basis for adjusting the dose of antithyroid drugs in patients with hyperthyroidism?
In patients with hyperthyroidism, the dose adjustment of antithyroid drugs should be based on serum T3/T4 levels rather than TSH.
223
What are the specific indications for estimating TSH receptor antibodies?
Specific indications for estimating TSH receptor antibodies include pregnant women with Graves' disease, isolated thyroid-associated orbitopathy/dermopathy, and predicting remission in Graves' disease during therapy.
224
What percentage of patients with Graves' disease have TSH receptor-stimulating antibodies?
TSH receptor-stimulating antibodies are present in 80-95% of patients with Graves' disease.
225
Which markers are non-specific for autoimmune thyroid disease?
Anti-TPO antibody and anti-Tg antibody are non-specific markers for autoimmune thyroid disease.
226
What are the common indications for thyroid scintigraphy?
Thyroid scintigraphy is commonly used to differentiate between subacute thyroiditis and Graves' disease. It is also required for patients with congenital hypothyroidism, functioning thyroid nodule, suspected ectopic thyroid, thyroid carcinoma, and midline neck swelling (thyroglossal cyst).
227
What is the purpose of using 99mTc pertechnetate in thyroid scans?
99mTc pertechnetate is used in thyroid scans as a marker to assess thyroid function and detect different thyroid disorders.
228
What are the available isotopes of iodine used in medical imaging?
The available isotopes of iodine used in medical imaging are 123I, 124I, 125I, and 131I.
229
What are the most common causes of subclinical hyperthyroidism?
The most common causes of subclinical hyperthyroidism are toxic multinodular goiter, toxic adenoma, and Graves' disease.
230
What are the associated risks of subclinical hyperthyroidism?
Subclinical hyperthyroidism is associated with increased cardiovascular risk, decreased bone mineral density, and possibly dementia.
231
When should subclinical hyperthyroidism be treated?
All patients with TSH <0.1 μIU/mL and age >65 years should be treated. Those with TSH <0.1 μIU/mL and age <65 years with symptoms of thyrotoxicosis and heart disease or osteoporosis should also be treated. In patients with TSH between 0.1 and 0.5 μIU/mL and age >65 years or TSH between 0.1 and 0.5 μIU/mL and age <65 years with comorbidities, treatment should be considered.
232
What is the recommended treatment for subclinical hyperthyroidism associated with toxic adenoma or toxic multinodular goiter?
The recommended treatment for subclinical hyperthyroidism associated with toxic adenoma or toxic multinodular goiter is radioactive iodine.
233
How should subclinical hyperthyroidism associated with Graves' disease be treated?
Subclinical hyperthyroidism associated with Graves' disease should be treated with low-dose antithyroid drugs.
234
What is thyroid storm?
Thyroid storm is a life-threatening condition characterized by exaggerated symptoms of thyrotoxicosis with multiorgan dysfunction.
235
What are the clinical clues to suggest the presence of thyroid storm?
Hyperpyrexia, disproportionate tachycardia, arrhythmias, and encephalopathy are the clinical clues to suggest the presence of thyroid storm.
236
What is the most common cause of hungry bone syndrome?
The most common cause of hungry bone syndrome (HBS) is parathyroidectomy for hyperparathyroidism.
237
What are the other causes of hungry bone syndrome?
The other causes of hungry bone syndrome include patients with rickets/osteomalacia who are replaced with vitamin D alone without calcium, untreated severe hyperthyroidism following thyroid surgery, correction of metabolic acidosis in patients with renal tubular acidosis, and after administration of antiresorptive therapy in patients with osteoblast metastasis.
238
What are the predictors of hungry bone syndrome in patients with primary hyperparathyroidism?
The predictors of hungry bone syndrome in patients with primary hyperparathyroidism include old age (>60 years), postmenopausal status, vitamin D deficiency, severe bone disease, high preoperative serum calcium and PTH, and large parathyroid adenoma.
239
How can hungry bone syndrome be prevented following parathyroidectomy?
Prior use of bisphosphonate reduces the risk of hungry bone syndrome by causing osteoclast apoptosis, suppressing bone remodeling, and preventing the entry of calcium into bone.
240
How can hypocalcemia due to hungry bone syndrome be differentiated from prior bisphosphonate therapy in a patient with primary hyperparathyroidism postoperatively?
Low serum phosphate is characteristic of hungry bone syndrome, while rising serum alkaline phosphatase (ALP) favors hypocalcemia due to hungry bone syndrome.
241
How is hungry bone syndrome treated?
Frequent monitoring of serum calcium is advised, and with the development of symptomatic hypocalcemia or serum calcium <8.4 mg/dl, calcium supplementation should be initiated. Oral calcium and calcitriol should be administered to prevent hypercalcemia. In addition, vitamin D deficiency should be supplemented.
242
What are the indicators of resolution of hungry bone syndrome?
The indicators of resolution of hungry bone syndrome include normalization of serum calcium, phosphorous, ALP and bone turnover markers, healing of osteitis fibrosa cystica, and significant gain in bone mineral density (BMD).
243
How should a patient with primary hyperparathyroidism be followed postoperatively?
Postoperatively, serum calcium, phosphorus, and alkaline phosphatase should be monitored.
244
What are some causes of low IGF1 in patients with acromegaly?
Some causes of low IGF1 in patients with acromegaly include uncontrolled diabetes mellitus, hypothyroidism, hypogonadism, hepatic or renal failure, malnutrition, systemic illness, catabolic states, and oral estrogen therapy.
245
Why is IGFBP3 not used in the diagnosis of acromegaly?
IGFBP3 is not used in the diagnosis of acromegaly because its levels in patients with acromegaly frequently overlap with those found in normal individuals, and it is less tightly regulated by GH compared to IGF1.
246
What are the alterations in GH dynamics in acromegaly?
Patients with active acromegaly have an increase in frequency and amplitude of GH pulses, non-suppressible GH after glucose load, elevated levels of IGF1 and IGFBP3, and the reappearance of the GH response to TRH.
247
Is further testing required for confirmation of the diagnosis in a patient with clinical features of acromegaly and elevated serum IGF1?
Yes, GH suppression test is required to confirm the diagnosis, as IGF1 is a screening test. The inability to suppress serum GH to <1 ng/mL after oral glucose load is diagnostic of active acromegaly.
248
What are some causes of non-suppressible GH after glucose load other than acromegaly?
In addition to acromegaly, uncontrolled diabetes, hypothyroidism, puberty, pregnancy, depression, chronic liver or renal disease, and anorexia nervosa are associated with non-suppressible GH after glucose load.
249
How does glucose suppress growth hormone?
Acute hyperglycemia suppresses GH by increasing somatostatin tone, suppressing ghrelin secretion, and modulating various neurotransmitters in the hypothalamus. However, in patients with acromegaly, the suppressive effect of glucose on GH secretion is mitigated.
250
What is the 'gold standard' test for the diagnosis of GH excess?
The 'gold standard' test for the diagnosis of GH excess is the GH suppression test after a 75g oral glucose load.
251
What is pasireotide?
Pasireotide is a somatostatin receptor analogue which acts on receptor subtypes SSTR1, SSTR2, SSTR3, and SSTR5, with the highest binding affinity for SSTR5.
252
What is the rationale for using pasireotide in patients with Cushing’s disease?
Pasireotide is used in patients with Cushing’s disease because corticotropinoma predominantly expresses SSTR5 receptor, which is the receptor subtype with the highest binding affinity for pasireotide.
253
What was the efficacy of pasireotide in normalizing urine free cortisol in the study mentioned?
In the study, pasireotide was able to normalize urine free cortisol in 15% and 26% of patients at doses of 600 and 900 μg twice daily, respectively.
254
What is the most common adverse event observed during the study of pasireotide?
The most common adverse event observed during the study was drug-induced hyperglycemia in 70%, due to inhibition of incretin secretion/effect.
255
What is the benefit of preoperative medical therapy in patients with Cushing’s syndrome?
The aim of preoperative medical treatment in patients with Cushing’s syndrome is to restore eucortisolemia and minimize immediate peri- and postoperative complications.
256
Is there a possibility of early recovery of the hypothalamo-pituitary-adrenal axis with preoperative medical treatment?
There is a possibility of early recovery of the hypothalamo-pituitary-adrenal axis with preoperative medical treatment, leading to shorter duration of post-surgery adrenal insufficiency.
257
What is the role of combined medical therapy in patients with pituitary Cushing’s syndrome?
The role of combined medical therapy in patients with pituitary Cushing’s syndrome is to achieve rapid eucortisolemia, reduce adverse effects, and target multiple sites affected by the condition.
258
What are the definite indications for bilateral adrenalectomy in patients with Cushing’s syndrome?
The definite indications for bilateral adrenalectomy in patients with Cushing’s syndrome are AIMAH and PPNAD.
259
How is hypoglycemia classified in patients with diabetes?
Hypoglycemia is classified in patients with diabetes as severe, documented symptomatic, asymptomatic, probable symptomatic, and relative hypoglycemia.
260
Why is the classification of hypoglycemia important?
The classification of hypoglycemia is important because it helps to provide uniformity in defining hypoglycemia as an adverse event with antidiabetic drugs in scientific studies.
261
What should be the treatment strategies for hypoglycemia?
The treatment strategies for hypoglycemia should be individualized. Patients with adrenergic symptoms should be treated with oral glucose tablets or fruit juice or candy. Blood glucose should be re-estimated after 15–20 min.
262
How should hypoglycemia be managed in patients receiving basal insulin or long-acting sulfonylureas?
Patients receiving basal insulin or long-acting sulfonylureas require close monitoring for at least 24–72 h.
263
What should be administered to patients with hypoglycemia and cognitive dysfunction?
Patients with hypoglycemia and cognitive dysfunction should be administered 25 g of dextrose intravenously to rapidly normalize blood glucose and may require continuous administration of 5% dextrose, depending upon improvement in sensorium and antidiabetic treatment received.
264
Does diabetes increase the risk of infection?
Infections are more severe and aggressive in patients with diabetes, but it is debatable whether diabetes per se increases the risk of infections.
265
What are the common infections seen exclusively in patients with diabetes?
Common infections seen exclusively in patients with diabetes include rhino-orbital-cerebral mucormyosis, malignant otitis externa, emphysematous pyelonephritis, and emphysematous cholecystitis.
266
What are the causes of anemia in diabetes?
Causes of anemia in diabetes include diabetic kidney disease, autonomic neuropathy-related gastroparesis, blind-loop syndrome, and drugs used in the management of T2DM.
267
What is the indication for using Pegvisomant?
Pegvisomant is indicated in SRL therapy-resistant acromegaly and in patients of acromegaly with worsening of glycemic status on SRL therapy.
268
How does Pegvisomant prevent the action of GH?
Pegvisomant prevents the action of GH by preventing the binding of site 1 of native GH to its corresponding site on the receptor.
269
What are the adverse effects associated with pegvisomant therapy?
The adverse effects associated with pegvisomant therapy are hepatotoxicity and lipodystrophy.
270
How frequently should liver function tests be monitored when starting pegvisomant therapy?
Liver function tests should be monitored monthly for the initial 6 months after starting pegvisomant and biannually thereafter.
271
What should be done if the tumor size is stable after starting pegvisomant therapy?
If the tumor size is stable after starting pegvisomant therapy, tumor size should be monitored by MRI annually.
272
What is the advantage of combining somatostatin receptor ligands with pegvisomant?
The advantage of combining somatostatin receptor ligands with pegvisomant is effective control of GH and IGF1 levels, decreased incidence of dysglycemia, lesser requirement of pegvisomant dose, and reduction in the risk of increase in tumor size.
273
What is the recommended test for assessing the efficacy of medical management in patients with acromegaly?
The recommended tests for assessing the efficacy of medical management in patients with acromegaly are random GH and serum IGF1 levels.
274
What is the rate of discordance between GH and IGF1 levels on somatostatin receptor analogue therapy?
The rate of discordance between GH and IGF1 levels on somatostatin receptor analogue therapy is 48%.
275
What are the clinical manifestations of Bartter's syndrome?
The clinical manifestations of Bartter's syndrome include polyuria, polydipsia, muscle weakness, growth retardation, and nephrocalcinosis.
276
What is the genetic inheritance pattern of Bartter's syndrome?
Bartter's syndrome is inherited in an autosomal recessive pattern.
277
What are the biochemical abnormalities seen in Bartter's syndrome?
Biochemical abnormalities in Bartter's syndrome include defective epithelial transport of sodium and chloride, resulting in salt wasting, hypokalemia, and increased prostaglandin E levels.
278
Which transporter/channel/pump is affected in Type 1 Bartter's syndrome?
In Type 1 Bartter's syndrome, inactivating mutations occur in the sodium–potassium–chloride co-transporter (NKCC2).
279
What is the treatment approach for Bartter's syndrome?
Treatment for Bartter's syndrome includes liberal salt intake, supplementation of potassium and magnesium, use of non-steroidal anti-inflammatory drugs, and the administration of spironolactone or amiloride.
280
What are the clinical manifestations of Gitelman's syndrome?
The clinical manifestations of Gitelman's syndrome include salt wasting, hypokalemia, metabolic alkalosis, hypomagnesemia, and elevated PAC and PRA levels. Symptoms commonly include polyuria, weakness, and fatigue.
281
What is the genetic inheritance pattern of Gitelman's syndrome?
Gitelman's syndrome is inherited in an autosomal recessive pattern.
282
What is the cause of electrolyte abnormalities in Gitelman's syndrome?
Electrolyte abnormalities in Gitelman's syndrome are caused by inactivating mutations of the thiazide-sensitive sodium chloride co-transporter (NCCT) in the distal convoluted tubule, resulting in salt wasting and hypokalemia.
283
What is the difference between whole venous blood and venous plasma glucose?
The whole venous blood glucose is approximately 10–15% lower than venous plasma glucose.
284
What percentage of blood volume is constituted by proteins?
20%
285
Why is whole venous blood glucose lower than venous plasma glucose?
Because 20% of blood volume constituted by proteins is inaccessible to glucose.
286
Which glucose concentration is recommended by WHO and ADA for the diagnosis of diabetes?
Plasma glucose
287
What are the characteristics used to suspect MODY?
Onset of diabetes <25 years of age with strong family history of diabetes particularly in three successive generations with onset of disease <40 years of age.
288
What should be considered to differentiate MODY from T1DM and young onset T2DM?
The presence of ketosis/ketoacidosis, requirement of insulin since the diagnosis, lack of family history of diabetes, undetectable C peptide, and islet antibody positivity.
289
What are the common types of MODY?
There are thirteen forms of MODY, but the common six types are Hepatocyte nuclear factor-4α, Glucokinase gene, Hepatocyte nuclear factor-1α, Insulin promoter factor 1 (IPF/PDX1), Hepatocyte nuclear factor-1β, and Neurogenic differentiation factor-1.
290
Why do patients with MODY not manifest ketosis/ketoacidosis?
Patients with MODY do not have absolute insulin deficiency.
291
Why is it important to diagnose MODY?
MODY patients respond well to therapy with sulfonylureas/insulin, and insulin sensitizers like metformin and pioglitazone are less effective. Diagnosis of MODY is also important in genetic counseling.
292
What is the earliest abnormality in T2DM?
Impaired pulsatile insulin secretion
293
What can manifest as postprandial hypoglycemia in patients with prediabetes/early diabetes?
Relative hyperinsulinemia
294
How much ingested calcium is excreted in feces?
800 mg
295
How much absorbed calcium enters into circulation?
200 mg
296
What is the net excretion of calcium in urine per day, regardless of calcium intake?
200 mg
297
What is the net calcium balance in a healthy individual with an adequate intake of calcium?
nil
298
Why is there an increase in calcium requirement with advancing age?
There is an increase in calcium requirement due to age-related decline in 1α-hydroxylase activity, decreased absorption of calcium, reduced sensitivity to 1,25(OH)2D, low gastric acid output, and the use of proton pump inhibitors.
299
Why does calcium supplementation lead to increased cardiovascular risk?
Calcium supplementation is associated with increased cardiovascular risk due to the acute rise in serum calcium levels, release of proinflammatory cytokines, elevated FGF23 levels, vascular calcification, suppression of endogenous 1,25(OH)2D, and activation of the renin-angiotensin-aldosterone system (RAAS).
300
What is FGF23?
FGF23 is a peptide secreted by osteocytes that is involved in phosphate homeostasis. It inhibits the translocation of sodium phosphorus co-transporter in the proximal convoluted tubule and decreases intestinal phosphate reabsorption.
301
What is Klotho?
Klotho is a gene that encodes a protein present in three forms: transmembrane klotho, secreted klotho, and soluble klotho. It acts as a co-receptor for FGF23, resulting in phosphaturia, suppression of renal 1α-hydroxylase and PTH, and has antiaging and anti-IGF1 effects.
302
What are some movement disorders associated with hypothyroidism?
Some movement disorders associated with hypothyroidism include ataxia, hemichorea, and pseudoparkinson like syndrome.
303
What are some manifestations of peripheral nervous system involvement in hypothyroidism?
Manifestations of peripheral nervous system involvement in hypothyroidism include compressive neuropathies (such as carpal tunnel syndrome and tarsal tunnel syndrome), peripheral neuropathy with thickened nerves, and rarely autoimmune demyelinating neuropathies.
304
What is 'myxedema madness'?
'Myxedema madness' is a severe neuropsychiatric manifestation of long-standing untreated primary hypothyroidism.
305
What are the musculoskeletal manifestations of hypothyroidism?
Musculoskeletal manifestations of hypothyroidism include delayed deep-tendon reflexes, proximal myopathy, calf hypertrophy, arthralgia, and rarely myoedema.
306
Why are deep-tendon reflexes delayed in patients with hypothyroidism?
Deep-tendon reflexes are delayed in patients with hypothyroidism due to selective muscle fiber atrophy, decreased Na+/K+-ATPase activity, reduced expression of myosin ATPase, impaired contractility of actin-myosin complex, and defective sarcolemmal depolarization.
307
What reproductive system abnormalities can occur in women with hypothyroidism?
Women with hypothyroidism may experience delayed puberty, primary amenorrhea, menorrhagia, large multicystic ovaries, menstrual irregularities, premature ovarian failure, and infertility.
308
How does hypothyroidism influence the reproductive system in women?
Hypothyroidism can cause oligo- or amenorrhea, menorrhagia, and infertility in women. These abnormalities may be due to defects in GnRH pulsatility, hyperprolactinemia, altered estrogen metabolism, and impaired oocyte maturation.
309
Why is there hyperprolactinemia with hypothyroidism?
Hyperprolactinemia in hypothyroidism can be caused by increased TRH-mediated prolactin secretion, decreased dopaminergic tone, and reduced prolactin clearance. It can also be associated with secondary hypothyroidism in certain cases.
310
What are some examples of diabetic complications mentioned in the course notes?
Some examples of diabetic complications mentioned in the course notes are Dupuytren's contracture, carpal tunnel syndrome, and stenosing flexor tenosynovitis (trigger finger).
311
How can limited joint mobility (LJM) be assessed in patients with diabetes?
Limited joint mobility (LJM) can be assessed either by the prayer sign or table test.
312
What is the Brink-Starkman classification used for?
The Brink-Starkman classification is used to define the severity of limited joint mobility (LJM).
313
What is the suggested reading material mentioned in the course notes?
The suggested reading material mentioned in the course notes includes 'Endocrinology: Adult and Pediatric', 'Harrison's Principles of Internal Medicine', and 'Williams Textbook of Endocrinology: Expert Consult'.
314
What is diabetic nephropathy also known as?
Diabetic nephropathy is also known as diabetic kidney disease (DKD).
315
Do all patients with diabetes develop DKD?
No, not all patients with diabetes develop DKD. Approximately 5-40% of patients with type 2 diabetes mellitus (T2DM) develop DKD, while 25-40% of patients with type 1 diabetes mellitus (T1DM) develop DKD.
316
What is the normal range of 24-hour urinary protein excretion in a healthy adult?
In a healthy adult, the normal range of 24-hour urinary protein excretion is less than 150 mg/day.
317
What is microalbuminuria and how is it defined?
Microalbuminuria is defined as 24-hour urinary albumin excretion of 30-299 mg/day, urinary albumin excretion rate of 20-199 μg/min, or spot urinary albumin/creatinine ratio of 30-299 mg/g of creatinine.
318
What medications should be avoided in patients with PPGL due to the risk of hypertensive crisis?
Atropine and anesthetics like fentanyl, ketamine, morphine, halothane, and desflurane should be avoided.
319
What is the preferred treatment for pheochromocytoma?
Surgical treatment is the preferred modality after adequate α and β blockade.
320
What is the recommended surgical approach for pheochromocytoma <6 cm?
Laparoscopic adrenalectomy is the treatment of choice.
321
What should be done to manage intraoperative hypertension during pheochromocytoma surgery?
Intraoperative hypertension can be treated with nitroprusside infusion and arrhythmias with short-acting β-blockers like esmolol or lignocaine.
322
How should a patient with pheochromocytoma be monitored postoperatively?
Pulse rate, blood pressure, and blood glucose should be monitored. Hypotension should be managed with fluids, whereas hypertension with diuretics.
323
What should be done for biochemical testing after surgical treatment of pheochromocytoma?
Biochemical testing for urine or plasma metanephrine and normetanephrine should be done after 2–4 weeks of surgery. If cured, annual biochemical testing is recommended.
324
What are the causes of persistent hypertension despite curative surgery of pheochromocytoma?
Persistent hypertension may be due to resetting of baroreceptor tone, irreversible vascular alteration, structural kidney changes, inadvertent ligation of renal artery, or coexisting essential hypertension.
325
What was the diagnosis for the 24-year-old lady with hypertension, hypokalemia, and uncontrolled BP?
The diagnosis was primary hyperaldosteronism (primary aldosteronism).
326
What is the effectiveness of external beam radiation therapy (EBRT) compared to oral prednisolone in the management of clinically active thyroid-associated orbitopathy (TAO)?
EBRT has been shown to be as effective as oral prednisolone in the management of clinically active TAO as mono-therapy.
327
What is the response rate when radiotherapy and glucocorticoids are used together in the management of TAO?
The response rate increases by approximately 10% when radiotherapy and glucocorticoids are used together compared to glucocorticoids alone.
328
Who generally responds better to treatment in TAO?
Patients with recent-onset disease respond better than those with long-standing TAO.
329
What is a predictor of a favorable outcome in TAO?
A good clinical response within a week of initiating glucocorticoids usually predicts a favorable outcome.
330
Who are poor responders to glucocorticoid therapy in TAO?
Smokers and those with persistently elevated TRAb levels are poor responders to glucocorticoid therapy in TAO.
331
What are the limitations of intravenous methylprednisolone therapy for TAO?
Intravenous methylprednisolone therapy for TAO is associated with a failure of response in approximately 20%, relapse in 10–20%, and progression of dysthyroid optic neuropathy in 5% of patients.
332
What is the role of rituximab in the treatment of TAO?
Rituximab, a chimeric mouse–human monoclonal antibody against CD20, is effective in TAO despite being primarily active against B cells, as B cells contribute to orbitopathy.
333
What are the indications for orbital decompression in the management of TAO?
Orbital decompression is indicated in dysthyroid optic neuropathy, corneal breakdown, globe subluxation not responding to glucocorticoids, and disfiguring exophthalmos for cosmetic reasons in patients with inactive disease.
334
What is the cause of edema in a patient with hyperaldosteronism?
Edema is characteristically absent in patients with hyperaldosteronism due to the "escape effect", but its presence may indicate congestive cardiac failure or renal failure.
335
Should all patients with hypertension be screened for primary aldosteronism?
Prevalence of primary aldosteronism in unselected hypertensive patients is around 5-13%. Screening is recommended for patients with hypertension at a young age (<20 years), severe hypertension (BP >160/100 mmHg), drug-resistant hypertension, hypertension with hypokalemia, and hypertension with adrenal incidentaloma.
336
What are the clinical manifestations of primary aldosteronism?
The clinical manifestations of primary aldosteronism may include severe diastolic hypertension with target organ damage, fatigue, muscle weakness, polyuria, polydypsia, periodic paralysis, ventricular arrhythmias, and dysglycemia.
337
What are the endocrine causes of recurrent paraparesis?
The endocrine causes of recurrent hypokalemia accompanied by paraparesis include thyrotoxic periodic paralysis, primary aldosteronism, ectopic ACTH-secreting tumors, and renal tubular acidosis.
338
Why is hypertension a feature of primary aldosteronism?
Hypertension in primary aldosteronism is due to increased sodium reabsorption, extracellular volume expansion, increased peripheral vascular resistance, endothelial dysfunction, reduced NO synthase activity, and vascular fibrosis.
339
Why is target organ damage severe in primary aldosteronism?
Target organ damage is severe in primary aldosteronism due to aldosterone-induced expression of transforming growth factor β (TGF β), plasminogen activator inhibitor type 1 (PAI1), and collagen genes in vasculature and target organs.
340
What are the differences between aldosterone-producing adenoma and idiopathic bilateral adrenal hyperplasia?
The differences between aldosterone-producing adenoma and idiopathic bilateral adrenal hyperplasia include prevalence, age of onset, severity of hypertension, prevalence of hypokalemia, plasma aldosterone concentration, renin activity ratio, adrenal imaging results, and treatment options.
341
What is the predictive value of a postoperative day 1 fasting serum GH level <2 ng/mL in patients with acromegaly?
A postoperative day 1 fasting serum GH level <2 ng/mL is predictive of clinical and biochemical remission at 5 years.
342
When can GH-GTT be performed in patients with acromegaly postoperatively?
GH-GTT can be performed as early as the 1st week postoperatively.
343
What is the predictive value of a nadir GH level <1 ng/mL in patients with acromegaly at 5 years?
A nadir GH level <1 ng/mL is predictive of remission in 98% individuals at 5 years.
344
Why is immediate postoperative assessment of GH not favored according to current guidelines?
Immediate postoperative assessment of GH may be influenced by surgical stress-induced increase in GH secretion.
345
What should be monitored in the immediate postoperative period for patients with acromegaly?
Monitoring of urine output, serum electrolytes, blood glucose, and blood pressure is essential.
346
When should assessment for hypothalamo-pituitary-adrenocortical (HPA) axis be done after discontinuation of hydrocortisone in patients with acromegaly?
Assessment for HPA axis should be done after discontinuation of hydrocortisone for 24 hours between day 1 and 3 postoperatively.
347
When should thyroid function test be evaluated in patients with acromegaly postoperatively?
Thyroid function test should be evaluated after 6 weeks of surgery.
348
When is the ideal time to assess disease activity and residual pituitary function in patients with acromegaly postoperatively?
The ideal time to assess disease activity and residual pituitary function is 3 months after surgery.
349
What is the effect of obesity on testosterone levels in men?
Obesity in men is associated with functional hypogonadism as insulin resistance has an inhibitory effect on the hypothalamo-pituitary-testicular axis.
350
What is the role of 17β-hydroxysteroid dehydrogenase in adipose tissue?
17β-hydroxysteroid dehydrogenase activity in adipose tissue promotes peripheral conversion of androstenedione to testosterone.
351
What are the causes of bad obstetric history in patients with PCOS?
The causes of bad obstetric history in patients with PCOS are luteal phase defect, senescent ova fertilization, and dysglycemia.
352
Why is dysglycemia common in PCOS?
Dysglycemia is common in PCOS due to the high prevalence of insulin resistance, which causes placental vascular insufficiency resulting in fetal wastage.
353
What are the causes of infertility in PCOS?
The causes of infertility in PCOS are chronic anovulation, presence of senescent ova, hostile cervical mucus, and an unfavorable endometrial environment.
354
How can a diagnosis of PCOS be established?
A diagnosis of PCOS can be established based on clinical and biochemical hyperandrogenism, menstrual irregularity, and ultrasonography according to various guidelines.
355
What are the lacunae in the diagnostic criteria used for defining PCOS?
The lacunae in the diagnostic criteria for PCOS include ethnic variability in quantifying hirsute score, lack of assessment of tissue sensitivity to androgens, alterations in androgen levels with age, and non-standardization of androgen assays across laboratories.
356
How does adolescent PCOS differ from adult PCOS?
In adolescent PCOS, menstrual irregularity should not be considered as a diagnostic criterion unless it persists beyond 2 years after the onset of menarche. Hirsutism as assessed by the Ferriman-Gallaway score and Rotterdam ultrasound criteria are also not validated in adolescents.
357
What is the definition of remission in Cushing's syndrome?
Remission can be defined as resolution of clinical stigmata of Cushing’s and achievement of eucortisolemia with recovery of hypothalamo–pituitary–adrenal axis or hypocortisolemia requiring long-term glucocorticoid replacement.
358
What is the probability of recurrence of the disease for microadenomas at 10 years?
The probability of recurrence is 10–20% at 10 years for microadenomas.
359
How is persistence of disease defined in pituitary Cushing's syndrome?
Persistence of disease (failed surgery) is defined as no resolution of clinical and/or biochemical hypercortisolemia 6–12 weeks postoperatively or reappearance of clinical and/or biochemical hypercortisolemia within 1 year.
360
What is the definition of recurrence in pituitary Cushing's syndrome?
Recurrence is the resurgence of clinical and/or biochemical hypercortisolemia after being in remission for at least 1 year postoperatively.
361
What is the importance of immediate postoperative 0800h plasma cortisol?
An immediate postoperative 0800h plasma cortisol <50 nmol/L is the best predictor of long-term remission with a recurrence rate of approximately 10% at 10 years.
362
What does an immediate postoperative 0800h plasma cortisol >140 nmol/L suggest?
A 0800h plasma cortisol >140 nmol/L in the immediate postoperative period suggests a lower probability of achieving remission.
363
What are the cutoffs of serum cortisol for defining adrenal insufficiency?
Patients with a 0800h cortisol <100nmol/L require hydrocortisone supplementation irrespective of presence or absence of symptoms, whereas those with a serum cortisol >350 nmol/L can be followed up without any replacement.
364
What should be assessed during the follow-up of a patient with pituitary Cushing's syndrome after TSS?
During the follow-up, the adequacy of glucocorticoid supplementation, presence of Cushing's stigmata, and 0800h cortisol levels should be assessed.
365
What is milk-alkali syndrome?
Milk-alkali syndrome is a triad of PTH-independent hypercalcemia, metabolic alkalosis, and renal insufficiency caused by the intake of a large amount of calcium.
366
What are the three main components of milk-alkali syndrome?
The three main components of milk-alkali syndrome are PTH-independent hypercalcemia, metabolic alkalosis, and renal insufficiency.
367
What factors contribute to hypercalcemia in milk-alkali syndrome?
Hypercalcemia in milk-alkali syndrome is due to increased supplemental calcium intake, enhanced intestinal absorption of calcium, reduced reposition of calcium into bone, and decreased renal excretion of calcium.
368
How does hypercalcemia occur in milk-alkali syndrome?
Hypercalcemia in milk-alkali syndrome occurs due to increased calcium intake, enhanced intestinal absorption of calcium, reduced reposition of calcium into bone, and decreased renal excretion of calcium.
369
What is the pathophysiology of milk-alkali syndrome?
The pathophysiology of milk-alkali syndrome involves enhanced intestinal absorption of calcium, reduced reposition of calcium into bone, and decreased renal excretion of calcium.
370
What is the treatment for milk-alkali syndrome?
The treatment for milk-alkali syndrome involves discontinuation of the offending agent, saline diuresis, and dialysis. Bisphosphonates should be avoided as they themselves are nephrotoxic.
371
What is hypercalcemic crisis?
Hypercalcemic crisis is characterized by severe hypercalcemia (>14 mg/dl) with signs and symptoms related to multiorgan dysfunction, predominantly neurological.
372
Why do all patients with severe hypercalcemia not present with hypercalcemic crisis?
Severity of symptoms of hypercalcemia does not exclusively depend on the absolute level of serum calcium, but also on the rapidity of rise in serum calcium. Hypercalcemic crisis is rare in patients with PHPT despite having severe hypercalcemia because the disease is insidious in onset and allows the homeostatic mechanisms to operate, thereby preventing the development of hypercalcemic crisis.
373
What is glucotoxicity?
Glucotoxicity is a metabolic phenomenon characterized by impaired insulin secretion (β-cell) and/or impaired insulin action (skeletal muscle, liver, and adipocytes) due to toxic effects of worsening hyperglycemia.
374
What are the mechanisms involved in β-cell dysfunction due to glucotoxicity?
The β-cell dysfunction is characterized by impaired glucose-stimulated insulin secretion as a consequence of decreased GLUT2 expression, oxidative stress, endoplasmic reticulum stress, hypoxia, and cytokine-induced apoptosis.
375
Define lipotoxicity.
Lipotoxicity is defined as the deleterious effects of increased free fatty acid (FFA) on β-cell (insulin secretion) and insulin target sites (muscle, liver, and adipocytes).
376
What causes increased free fatty acid (FFA) levels in lipotoxicity?
Increased free fatty acid is due to enhanced lipolysis as a consequence of insulin resistance at adipocytes.
377
What is the clinical relevance of gluco-lipotoxicity?
Early intensive treatment of hyperglycemia may reverse gluco-lipotoxicity and lead to improvement in β-cell function and insulin sensitivity.
378
What is the significance of early intensive treatment of hyperglycemia?
Early intensive treatment of hyperglycemia is beneficial for the preservation of β-cell function and results in a good 'legacy effect' (metabolic memory).
379
What organs/tissues are involved in the pathogenesis of T2DM according to the ominous octet?
The organs/tissues involved in the pathogenesis of T2DM according to the ominous octet are β-cell, muscle, liver, adipocyte, gastrointestinal tract, α-cell, kidney, and central nervous system.
380
What is the thrifty genotype hypothesis?
The thrifty genotype hypothesis suggests that certain genes involved in insulin release and fat storage were naturally selected during times of nutrient excess for survival advantage, but they have adverse effects in modern times of sustained food availability, leading to obesity, insulin resistance, and diabetes.
381
Why should bilateral adrenalectomy not be preferred in all patients with pituitary Cushing’s syndrome?
Bilateral adrenalectomy is not the treatment of choice in all patients with pituitary Cushing’s syndrome because it is associated with multiple risks and complications.
382
What are the advantages of preserving pituitary hormones after treatment for pituitary Cushing’s syndrome?
Preserving pituitary hormones is advantageous as it avoids the need for lifelong hormone replacement.
383
What is Nelson’s syndrome?
Nelson’s syndrome refers to the growth of a corticotropinoma after total bilateral adrenalectomy in a patient with pituitary Cushing’s syndrome.
384
What are the predictors of Nelson’s syndrome?
The predictors of Nelson’s syndrome include the presence of residual or de novo corticotropinoma prior to bilateral adrenalectomy, an increase in ACTH levels, and an aggressive histological subtype of corticotropinoma.
385
What is the recommended treatment for Nelson’s syndrome?
The treatment of choice for Nelson’s syndrome is transsphenoidal surgery, and in the case of macroadenomas, adjuvant radiotherapy may be advised.
386
What is the role of radiotherapy in treating pituitary Cushing’s syndrome?
Radiotherapy is a second-line option and may be effective in treating pituitary Cushing’s syndrome, but it takes time for the effects to be seen and is associated with adverse effects.
387
What are the possible medical treatments for Nelson’s syndrome?
Medical treatments for Nelson’s syndrome include cabergoline, somatostatin analogues, temozolomide, and sodium valproate.
388
Why is transsphenoidal surgery considered curative in some patients with pituitary Cushing’s syndrome?
Transsphenoidal surgery is considered curative in some patients with pituitary Cushing’s syndrome as it has a high success rate and may not require lifelong hormone replacement.
389
What is hyperaldosteronism?
Hyperaldosteronism is defined as increased secretion of aldosterone which may result in hypertension and/or hypokalemia.
390
What are the causes of hypertension with hypokalemia?
The causes of hypertension with hypokalemia include primary aldosteronism, secondary aldosteronism due to renovascular hypertension or renin-secreting tumors, and the action of excess cortisol on the mineralocorticoid receptor.
391
What are the causes of hypokalemia with metabolic alkalosis?
The causes of hypokalemia with metabolic alkalosis include the use of diuretics, primary aldosteronism, Bartter's syndrome, Cushing's syndrome, gastrointestinal loss (vomiting), and certain genetic conditions.
392
Does normokalemia exclude primary aldosteronism?
No, normokalemia does not exclude primary aldosteronism. Hypertension is always present in patients with primary aldosteronism, while hypokalemia is observed in only 30-40% of cases.
393
Why is normokalemia more common in patients with primary aldosteronism?
Normokalemia is more common in patients with primary aldosteronism because the development of hypokalemia requires severe and prolonged exposure to aldosterone excess, significant depletion of body potassium stores, adequate sodium intake, and overriding of potassium homeostatic mechanisms.
394
What is the effect of chronic inhibition of RAAS in patients undergoing curative surgery for hyperaldosteronism?
Chronic inhibition of RAAS during curative surgery for hyperaldosteronism can lead to hypoaldosteronism, resulting in hyperkalemia postoperatively.
395
What is the abnormality in glucose insulin homeostasis in patients with primary hyperaldosteronism?
The abnormality in glucose insulin homeostasis in patients with primary hyperaldosteronism is due to chronic hypokalemia-induced inhibition of insulin secretion and the adverse effect of excess aldosterone on insulin sensitivity.
396
What is the direct stimulatory effect of GH and hyperphosphatemia on parathyroid cells?
The direct stimulatory effect of GH and hyperphosphatemia on parathyroid cells is increased calcium absorption and decreased renal reabsorption of calcium.
397
What is the result of hypercalciuria in acromegaly?
The result of hypercalciuria in acromegaly is increased calcium absorption and decreased renal reabsorption of calcium.
398
What effect does GH have on bone mineral density (BMD) in acromegaly?
GH increases bone mineral density (BMD) at both the hip and vertebrae in eugonadal patients.
399
What factors contribute to the increased fracture risk in acromegaly patients?
The increased fracture risk in acromegaly patients is due to concurrent hypogonadism, secondary hyperparathyroidism, and poor bone microarchitecture despite increased BMD on DXA.
400
Why is colonoscopy advised in all patients with acromegaly?
Colonoscopy is advised in all patients with acromegaly because they have a higher risk of adenomatous polyps and mortality with colonic carcinoma than those without acromegaly.
401
What are the malignancies associated with acromegaly?
The malignancies associated with acromegaly are papillary thyroid carcinoma, infiltrating duct carcinoma of the breast, and melanoma.
402
Which organs are devoid of growth-promoting effects of GH?
The brain and eye are devoid of growth-promoting effects of GH.
403
What is the best screening test for the diagnosis of acromegaly?
The best screening test for the diagnosis of acromegaly is serum insulin like growth factor 1 (IGF1)
404
What is suppressed by hypercortisolemia?
suppressed by hypercortisolemia; this is evidenced by the development of hypocortisolemia after curative adenomectomy.
405
What is the expected level of ACTH in the contralateral petrosal sinus during IPSS?
ACTH levels are expected to be undetectable in the contralateral petrosal sinus during IPSS.
406
Why are ACTH levels measurable on the contralateral side in IPSS?
Neither anatomically nor functionally does the pituitary gland behave as right and left halves, resulting in mixing of blood within the gland and in cavernous sinuses (intercavernous venous mixing) that leads to measurable and stimulable ACTH on the contralateral side.
407
What does the table given below show?
The table given below shows the result of IPSS in a patient with a microadenoma on the left half of the pituitary gland and clearly shows a detectable level of ACTH even in the right petrosal sinus.
408
What does dynamic MRI of the sella localize in the patient?
Dynamic MRI of the sella localizes a 7 mm adenoma on the left half of the pituitary gland.
409
What is the sensitivity of dynamic MRI in localizing the source of ACTH excess?
The sensitivity of dynamic MRI in localizing the source of ACTH excess is approximately 70% with a positive predictive value of 86% (as correlated with histopathology), which further increases to 92% if the tumor size is >4mm.
410
What is the sensitivity of CRH-stimulated IPSS in lateralizing the source of ACTH excess?
The sensitivity of CRH-stimulated IPSS in lateralizing the source of ACTH excess is 98% with a positive predictive value of only 69%.
411
Where was the adenoma confined in the index case during surgery?
During surgery, the adenoma was confined to the left half of the pituitary gland.
412
What are some possible causes of weight loss in a patient with sarcoidosis?
Weight loss in a patient with sarcoidosis can be attributed to anorexia and nausea associated with hypercalcemia and possibly due to IL-6 and IFN-ϒ secreted from noncaseating granulomas.
413
What is the relationship between elevated ACE levels and sarcoidosis?
Elevated ACE levels are seen only in 60% of patients with active disease in sarcoidosis.
414
What percentage of patients with sarcoidosis may have nephrolithiasis?
10% of patients with sarcoidosis may have nephrolithiasis.
415
What is the initial management strategy for hypercalcemia?
Volume repletion followed by saline diuresis is the initial management strategy in hypercalcemia.
416
What is the role of glucocorticoids in the treatment of hypercalcemia associated with sarcoidosis?
Glucocorticoids are the definitive treatment for hypercalcemia associated with sarcoidosis. They inhibit macrophage 1α-hydroxylase and decrease the production of PTHrP, IFNϒ, and bone-resorbing cytokines.
417
Why should vitamin D supplementation be avoided in patients with chronic granulomatous disorders?
Vitamin D supplementation should be avoided in patients with chronic granulomatous disorders because they are at an increased risk of developing hypercalcemia due to upregulated 1α-hydroxylase activity in the macrophages.
418
How is hypercalcemia defined?
Serum calcium level above the reference range is considered as hypercalcemia.
419
What factors can influence serum calcium levels?
Application of tourniquet while sampling, hydration status, serum albumin, and analytical method can influence serum calcium levels.
420
What are the causes of hyperprolactinemia in primary hypothyroidism?
The causes of hyperprolactinemia in primary hypothyroidism are lactotrope hyperplasia due to increased TRH drive, decreased prolactin clearance, and suppressed dopaminergic tone.
421
What is the usual level of serum prolactin in hyperprolactinemia caused by primary hypothyroidism?
Serum prolactin levels usually do not exceed >100 ng/ml.
422
How long does it take for levothyroxine to normalize prolactin levels in primary hypothyroidism?
Treatment with levothyroxine normalizes prolactin levels in 6-12 weeks.
423
What are the physiological causes of lactotrope hyperplasia?
The physiological causes of lactotrope hyperplasia are pregnancy and lactation, mediated through estrogen.
424
What is the most common pathological cause of lactotrope hyperplasia?
The most common pathological cause of lactotrope hyperplasia is primary hypothyroidism.
425
What are the clinical features of hyperprolactinemia in women?
Clinical manifestations of hyperprolactinemia in women are menstrual irregularities, galactorrhea, and infertility.
426
What are the clinical features of hyperprolactinemia in men?
Men with hyperprolactinemia present with decreased shaving frequency, reduced libido, erectile dysfunction, and infertility.
427
How does hyperprolactinemia cause gonadal dysfunction in women?
Hyperprolactinemia inhibits GnRH pulse generator activity, suppresses gonadotropin secretion, impairs folliculogenesis, decreases estradiol production, interferes with ovulation, and causes luteal phase defects.
428
What treatment was offered to the patient with peri-pituitary edema?
The patient was offered conservative management.
429
What medication was used to treat the peri-pituitary edema?
The patient was treated with intravenous dexamethasone.
430
What is the rapid effect of cabergoline in patients with visual field defects?
Cabergoline rapidly improves visual field defects within hours of its use.
431
What is the risk associated with the use of cabergoline in patients with apoplexy?
The use of cabergoline in patients with apoplexy carries the risk of worsening apoplexy.
432
What is the topographical distribution of somatotropes and lactotropes in the pituitary gland?
Somatotropes are laterally placed and lactotropes are laterally placed in the pituitary gland.
433
What is the essential role of prolactin?
Prolactin is essential for galactopoiesis and plays a permissive role in mammo- genesis. It also has an important role in immune system and gonadal function.
434
How does prolactin mediate its action?
Prolactin binds with its receptor and activates the Janus kinase pathway, leading to signal transduction and activation of target genes.
435
What level of serum prolactin is considered hyperprolactinemia in women?
In women, a level of serum prolactin above 25 ng/ml is considered hyperprolactinemia.
436
What are the criteria for controlled disease after acromegaly surgery?
Normalization of serum IGF1 and random GH <1 ng/ml or nadir GH after glucose load <0.4 ng/ml
437
Why can the results of GH and IGF1 be discordant after surgery?
The disruption of neural or anatomical network of GH regulation after surgery can cause discordant results.
438
In acromegaly patients, what does a normal age-adjusted serum IGF1 with random GH >1 ng/ml after glucose load suggest?
A higher risk of recurrence and the need for close follow-up.
439
What does suppressed GH but elevated IGF1 levels in an acromegaly patient indicate?
Active disease that should be treated accordingly.
440
Which clinical features are irreversible in a patient with acromegaly after curative surgery?
Skeletal manifestations like prognathism, osteoarthritis, and kyphoscoliosis are usually irreversible.
441
When should primary medical treatment be considered in patients with acromegaly?
Primary medical therapy should be considered in high-risk patients, those who refuse surgery, and those with invasive macroadenoma without mass effects.
442
When is medical treatment discouraged as a primary modality for acromegaly?
Medical treatment should be discouraged in patients with microadenoma, where the cure rate after surgery is 80-90%.
443
What are the treatment options for acromegaly patients with active disease after transsphenoidal surgery?
The options include repeat surgery, medical therapy, and radiotherapy.
444
Why are patients with DKA phosphate depleted?
Patients with DKA are phosphate depleted due to insulin therapy promoting its transcellular shift.
445
What is dilutional hyponatremia and why is it seen in DKA?
Dilutional hyponatremia is low serum sodium levels seen in DKA patients due to the osmotic effects of glucose.
446
What causes hyperchloremic metabolic acidosis in DKA patients?
Hyperchloremic metabolic acidosis may occur in DKA patients due to overzealous saline administration.
447
Why is timely initiation of oral feeds encouraged in patients recovering from DKA?
Timely initiation of oral feeds in DKA patients helps in repletion of hepatic glycogen stores and restoration of gut flora.
448
After recovery from DKA, why does ketonuria persist?
Ketonuria persists after recovery from DKA due to the slow release of ketone bodies from adipose tissue.
449
What are the possibilities to be considered if a patient deteriorates after initial recovery from DKA?
Possibilities to consider if a patient deteriorates after initial recovery from DKA include cerebral edema, mucormycosis, infections, sepsis, and acute kidney injury.
450
Why are DKA patients predisposed to rhino-orbito-cerebral mucormycosis?
Patients with DKA are predisposed to rhino-orbito-cerebral mucormycosis because the fungi Mucor is angioinvasive and characteristically ferrophilic.
451
What were the symptoms that the patient presented with?
The patient presented with pain and swelling in the left knee and a lytic lesion in the upper part of the left tibia.
452
What was the diagnosis based on the histopathology report?
The histopathology report revealed a giant cell tumor.
453
What treatment did the patient receive for the giant cell tumor?
The patient underwent bone curettage with implantation of fibular graft and received localized radiation therapy through external beam radiotherapy.
454
What were the findings of the bone scan performed on the patient?
The bone scan showed multiple lytic lesions.
455
What were the patient's laboratory results for serum calcium, phosphate, alkaline phosphatase, iPTH, and 25(OH)D?
The patient had a corrected serum calcium level of 15.1 mg/dl, phosphate level of 2.4 mg/dl, alkaline phosphatase level of 943 IU/ml, iPTH level of 1,687 pg/ml, and 25(OH)D level of 13.2 ng/ml.
456
What was the diagnosis based on the 99mTc-sestamibi scan?
The 99mTc-sestamibi scan localized a right inferior parathyroid adenoma.
457
How was hypercalcemia managed preoperatively?
Hypercalcemia was managed with saline diuresis and intravenous zoledronic acid (5 mg).
458
What were the patient's laboratory results for serum calcium and phosphate postoperatively?
Postoperatively, the patient had symptomatic hypocalcemia with a serum calcium level of 6.7 mg/dl and phosphate level of 1.3 mg/dl.
459
What are the consequences of the loss of pulsatile insulin secretion in diabetes?
The loss of pulsatile insulin secretion is responsible for fasting hyperglycemia.
460
What is the role of first phase insulin secretion in diabetes?
Loss of glucose-induced first phase insulin secretion contributes to postprandial hyperglycemia.
461
How do incretins contribute to insulin secretion?
Incretins, such as GLP1 and GIP, potentiate glucose-mediated insulin secretion.
462
What are the major incretins?
The major incretins are glucagon-like peptide-1 (GLP1) and glucose-dependent insulinotropic peptide (GIP).
463
What are the effects of GLP1 on glucose homeostasis?
GLP1 delays gastric emptying, stimulates insulin release, inhibits glucagon secretion, and reduces hepatic glucose output and fasting hyperglycemia.
464
What is the incretin status in type 2 diabetes?
In type 2 diabetes, GLP1 levels may be either low (GLP1 deficiency) or normal (GLP1 resistance).
465
What is the glucose-glucagon axis?
The glucose-glucagon axis refers to the regulation of glucagon secretion by glucose levels in a healthy individual.
466
What is the Starling curve of the pancreas?
The term 'Starling curve' describes the beta-cell response to rising blood glucose levels.
467
What should be considered if a patient has a mildly elevated TSH in the diagnosis of secondary hypothyroidism?
The possibility of concurrent ACTH deficiency should be considered.
468
What is the role of thyroid peroxidase (TPO)?
TPO is a microsomal enzyme involved in oxidation, organification, and coupling, required for thyroid hormone synthesis.
469
What is the prime regulator of TPO activity?
TSH is the prime regulator of TPO activity.
470
What is the function of anti-TPO antibody?
Anti-TPO antibody is a surrogate marker of autoimmune thyroid disease and represents an 'epiphenomenon' of thyroid autoimmunity.
471
Why is serum T3 estimation not useful in the diagnosis of primary hypothyroidism?
Serum T3 remains within the normal range in patients with overt hypothyroidism due to increased T3 secretion by the thyroid gland and augmented peripheral T4 to T3 conversion by peripheral deiodinase type 2.
472
What are the regulators of T4 to T3 neogenesis?
Type 2 monodeiodinase, type 1 monodeiodinase, TSH, and GH are the regulators of T4 to T3 neogenesis.
473
How does amiodarone cause hypothyroidism?
Amiodarone contains a high level of iodine, which can lead to thyroid dysfunction.
474
How should amiodarone-induced hypothyroidism be managed?
Amiodarone-induced hypothyroidism should be treated with levothyroxine without discontinuation of amiodarone.
475
What is the clinical use of BMD?
BMD is used in clinical practice to predict fracture risk.
476
Name some disorders associated with high BMD and increased fracture risk.
Fluorosis, osteopetrosis, Paget’s disease (sclerotic form), osteoblastic skeletal metastasis, prolonged bisphosphonate therapy, and T2DM.
477
What does bone mineral content represent?
Bone mineral content represents the mineral mass expressed in grams.
478
How is bone mineral density measured?
Bone mineral density is measured as gm/cm3 (volumetric BMD as measured with quantitative CT) or gm/cm2 (areal BMD as measured by DXA).
479
What are the constituents of bone?
Bone is made up of cells (osteoblasts, osteoclasts, and osteocytes) and a matrix (inorganic components like calcium hydroxyapatite, phosphorus, and magnesium; organic components like collagen and non-collagenous proteins).
480
What are osteocytes?
Osteocytes are terminally differentiated osteoblasts that make up 90% of all bone cells. They act as mechanostats, produce sclerostin, and secrete FGF23.
481
What is bone remodeling?
Bone remodeling is a sequential process of bone formation and resorption due to crosstalk between osteoblasts and osteoclasts.
482
What is the difference between bone modeling and remodeling?
Bone modeling occurs during childhood and peripubertal period without preceding bone resorption, while bone remodeling involves resorption and formation of bone and begins after peripubertal period.
483
What were the symptoms exhibited by the patient?
The patient exhibited symptoms of acral enlargement, headache, hyperhidrosis, seborrhea, and diffuse hyperpigmentation.
484
What were the patient's vital signs at presentation?
At presentation, the patient had a blood pressure of 100/60 mm of Hg and was tachypneic.
485
What were the patient's blood glucose levels and HbA1c at presentation?
At presentation, the patient's blood glucose was 550 mg/dl and HbA1c was 17%.
486
What was the patient's insulin requirement during treatment?
During treatment, the patient had an insulin requirement of around 200 units per day initially, which gradually reduced to 100 units per day.
487
What were the hormonal workup results of the patient?
The hormonal workup showed abnormal levels of T4, TSH, 0800 h cortisol, ACTH, prolactin, testosterone, serum insulin-like growth factor 1 (IGF1), and growth hormone (GH).
488
What was the result of the MR imaging?
The MR imaging showed a sellar–suprasellar mass of 4.8 × 3.2 × 3.5 cm abutting the optic chiasm, and the visual field examination confirmed bitemporal hemianopia.
489
What was the final diagnosis of the patient?
The patient was diagnosed with acromegaly due to macrosomatotropinoma, with secondary diabetes, diabetic ketoacidosis, secondary hypothyroidism, and hypogonadism.
490
What was the postoperative day 2 serum GH level and cortisol level?
On postoperative day 2, the patient's serum GH level was 4 ng/ml and cortisol level was 450 nmol/L.
491
What can be used to relieve the symptoms of hypogonadism in patients with drug-induced hyperprolactinemia?
Gonadal steroids
492
What is the recommended treatment option for drug-induced hyperprolactinemia after appropriate consultation with a psychiatrist?
Switch to atypical anti-psychotic drugs like quetiapine or anti-psychotic drugs with dopamine agonist and antagonist activity like aripiprazole
493
Is treatment necessary for asymptomatic patients with drug-induced hyperprolactinemia?
No, treatment is not necessary for asymptomatic patients
494
What is the most common functioning pituitary tumor?
Prolactinoma
495
What are the common symptoms of prolactinoma in women?
Menstrual irregularities, galactorrhea, and infertility
496
What are the common symptoms of prolactinoma in men?
Symptoms of mass effects and features of hypogonadism
497
What is a 'giant' prolactinoma?
An adenoma larger than 4 cm in size or with a volume larger than 10 cm3, usually associated with serum PRL >1,000 ng/ml
498
What familial syndromes are associated with prolactinoma?
Multiple endocrine neoplasia type 1, familial isolated pituitary adenoma (AIP mutations), and rarely SDHB mutations (in association with paraganglioma)
499
What are some disorders related to adrenal steroidogenesis?
Congenital adrenal hyperplasia
500
What are some malignant disorders related to adrenal glands?
Primary adrenal lymphoma, metastasis
